here you go

Search Results

You searched for 'SOP'. Your search returned 39 results.

Palliative radiotherapy in addition to self expanding metal stent for improving outcomes of dysphagia and survival in advanced oesophageal cancer (ROCS)

Summary:
The single most distressing symptom for more than 70% of patients with oesophageal cancer is difficulty in swallowing (dysphagia) caused by blockage of the gullet by a tumour. This causes severe restrictions on food intake, physical activity, social functioning and overall quality of life. Amongst the more effective treatments for improving swallowing, is the insertion of a metal stent (Self Expanding Metal Stent or SEMS) across the blocked part, which then self-expands to open up the gullet. The addition of radiotherapy may help to improve the problems caused by dysphagia and provide an additional survival benefit.
The purpose of this study is to test the impact of adding radiotherapy to SEMS on:
i) the length of time swallow remains improved for
ii) quality of life
iii) survival

Patients will be eligible to take part in the trial if they have oesophageal cancer, are in need of SEMS because of dysphagia, are aged 16 years or older, have been clinically assessed to be able to receive radiotherapy, have an expected survival of at least 12 weeks and are able to give written informed consent.
Four hundred and ninety-six patients will be randomised to receive either SEMS alone or SEMS with radiotherapy. The radiotherapy will be given as an outpatient either as five treatments (one per day) over one week, or ten treatments over two weeks. Questionnaires will be completed before treatment, within one week of stent insertion and then four
weeks after stent insertion until death to assess quality of life and cost. Interviews will be held with a sub-set of trial participants at three time points to explore their experiences whilst on the trial. Interviews will also be held with patients who do not consent to take part in the trial to explore their reasons for non-consent.

Inclusion criteria:
1. Histological confirmation of oesophageal carcinoma excluding small cell histology
2. Not suitable for radical treatment (oesophagectomy or radical chemoradiotherapy) either because of patient choice or medical reasons
3. Dysphagia clinically assessed as needing stent as primary treatment of the dysphagia
4. Age 16 or over
5. Discussion and treatment decision for SEMS placement made by an Upper GI multi-disciplinary team
6. Clinician assessment of ability to attend for radiotherapy
7. Expected survival of at least 12 weeks
8. Written informed consent

Exclusion criteria:
1. Histology of small cell carcinoma type
2. Tumour length of greater than 12 cm
3. Tumour growth within 2 cm of the upper oesophageal sphincter
4. Endoscopic treatment of the tumour, other than dilatation, planned in the peri-stent period
5. Presence of a tracheo-oesophageal fistula
6. Presence of a pacemaker
7. Previous radiotherapy to the area of the proposed radiotherapy field
8. Endoscopic treatment of the tumour (e.g. laser) in the immediate peri-stenting period
9. Pregnancy

Principal Investigator for this trial: Mr Ravinder Vohra

Research Ethics Committee Reference: 12/WA/0230

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Randomised Clinical Trial of neoadjuvant and adjuvant chemotherapy (MAGIC regimen) vs. neoadjuvant chemoradiation (CROSS protocol) in adenocarcinoma of the oesophagus and oesophago-gastric junction.

Summary:
Cancer of the oesophagus (gullet/food pipe) and oesophagogastric junction (junction between the oesophagus and stomach) have increased in incidence in the West over the last 25 years. Oesophageal cancer is now the 9th most common cancer in the UK, accounting for 3% of all new cases. The aim of this research study is to compare and evaluate two established treatments for oesophageal cancer in order to establish if one treatment is superior to the other. The research group believe it is not currently clear which regimen is of greatest benefit to patients. These 2
regimens have been tested in previous randomised trials (MAGIC & CROSS). The 2 treatments are either
chemotherapy before and after surgery, or chemotherapy with radiotherapy before surgery. Both treatments are
standard and have been in use as treatments for oesophageal cancer for several years. 594 patients with
oesophageal and oesophagogastric junction cancer will be randomly allocated to these 2 treatments. During the trial patients will have a variety of clinical assessments and will complete health-related questionnaires. Following treatment they will be followed up for 3 years. The main objective of this trial is to look at overall survival. Secondary objectives are patient quality of life, complications and relief of swallowing problems.

Inclusion criteria:
1. Histologically-verified adenocarcinoma of the oesophagus or oesophagogastric junction based on OGD.
2. CT-18FDG-PET in all patients and EUS, if feasible
3. Staging laparoscopy will be performed for tumours of the abdominal oesophagus, junction and proximal stomach i.e. AEG II and AEG III (at the investigator’s discretion)
4. Pre-treatment stage cT23, N03, M0
5. No prior abdominal or thoracic radiotherapy
6. Male/female patients aged >18 years
7. ECOG Performance Status 0, 1 or 2
8. ASA Grading I-II
9. Adequate cardiac function. For all patients an ejection fraction of ≥ 50% is required. If patients have a known
significant cardiac history(e.g. known ischaemic disease, cardiomyopathy) an ejection fraction >50% and cardiac clearance by a consultant cardiologist for major surgery and cancer therapies is required. Where necessary, the Chief Investigator should be consulted to discuss the patient’s eligibility.
10. Adequate respiratory function. Patients should have pulmonary function tests completed with FEV1 >1.5L
11.Adequate bone marrow function: absolute neutrophil count (ANC) >1.5×109/l; white blood cell count >3×109/l;
platelets >100×109/l; haemoglobin (Hb) >9g/dl (can be posttransfusion).
12.Adequate renal function: glomerular filtration rate >60ml/minute calculated using the Cockcroft-Gault
Formula
13.Adequate liver function: serum bilirubin Exclusion criteria:
1. Tumours of squamous histology.
2. Patients with advanced inoperable or metastatic oesophageal, junctional or gastric adenocarcinoma.
3. Any prior chemotherapy for gastrointestinal cancer.
4. Prior abdominal or thoracic radiation.
5. Patients who are unfit for surgery or cancer treatments based on cardiac disease.
6. Patients with acute systemic infections.
7. Patients who are receiving treatment with Sorivudine or it’s chemical related analogues, such as Brivudine, which is contraindicated with capecitabine and 5-Fluorouracil administration.
8. Clinical COPD with significant obstructive airways disease classified by FEV1 Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
10. Known positive tests for human immunodeficiency virus (HIV) infection, acute or chronic active hepatitis B infection.
11. Any other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
12. Women who are pregnant or who are breastfeeding.

Principal Investigator for this trial: Mr Simon Leslie Parsons

Research Ethics Committee Reference: 14/EM/1284

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Evaluation of a NonEndoscopic Immunocytological Device (Cytosponge) for Barrett’s Esophagus Screening in a CaseControl Study (BEST 2)

Summary:
Oesophageal cancer is an increasing problem in the western world with a high mortality. Outcomes can be dramatically improved by detecting the precancerous conidtion called Barrett’s oesophagus. We have developed a screening test (Cytosponge coupled with a molecular test) for Barrett’s oesophagus. We now want to use this device to categorise individuals according to their risk for developing cancer. To do this we will use different molecular tests applied to cells collected by the Cytosponge device. The study is a case: control study design in which the cases will be patients with known Barrett’s Oesophagus (BE) and controls individuals with reflux or indigestion (dyspepsia) symptoms referred for endoscopy. Four centres with expertise in Barrett’s oesophagus will recruit patients. All participants will swallow the Cytosponge device prior to having an endoscopy. The Cytosponge will be processed for a number of different biomarkers. The results will be compared with the endoscopy findings.

Inclusion criteria:
Inclusion · Any participant 18 years and above clinically fit for an endoscopy with Barrett’s oesophagus (Cases) with or without upper GI symptoms · Any participant 18 years and above clinically fit for an endoscopy with upper GI symptoms of reflux or dyspepsia as an indication for endoscopy/gastroscopy (Controls) · Ability to provide informed consent

Exclusion criteria:
Exclusion criteria · Individuals with a diagnosis of an oropharynx, oesophageal or gastrooesophageal tumour, or symptoms of dysphagia, · oesophageal varices, stricture or requiring dilatation of the oesophagus · on anticoagulation therapy/medication (warfarin, clopridogrel,heparin or tinzaparin). · Individuals who have had a myocardial infarction or any cardiac event less than six months ago. · Individuals who have had a cerebrovascular event Principal Investigator for this trial: Dr Krish Ragunath

Research Ethics Committee Reference: 10/H0308/71

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Evaluation of a NonEndoscopic Immunocytological Device (Cytosponge) for Barrett’s Esophagus Screening in a CaseControl Study (BEST 2)

Summary:
Oesophageal cancer is an increasing problem in the western world with a high mortality. Outcomes can be dramatically improved by detecting the precancerous conidtion called Barrett’s oesophagus. We have developed a screening test (Cytosponge coupled with a molecular test) for Barrett’s oesophagus. We now want to use this device to categorise individuals according to their risk for developing cancer. To do this we will use different molecular tests applied to cells collected by the Cytosponge device. The study is a case: control study design in which the cases will be patients with known Barrett’s Oesophagus (BE) and controls individuals with reflux or indigestion (dyspepsia) symptoms referred for endoscopy. Four centres with expertise in Barrett’s oesophagus will recruit patients. All participants will swallow the Cytosponge device prior to having an endoscopy. The Cytosponge will be processed for a number of different biomarkers. The results will be compared with the endoscopy findings.

Inclusion criteria:
Inclusion · Any participant 18 years and above clinically fit for an endoscopy with Barrett’s oesophagus (Cases) with or without upper GI symptoms · Any participant 18 years and above clinically fit for an endoscopy with upper GI symptoms of reflux or dyspepsia as an indication for endoscopy/gastroscopy (Controls) · Ability to provide informed consent

Exclusion criteria:
Exclusion criteria · Individuals with a diagnosis of an oropharynx, oesophageal or gastrooesophageal tumour, or symptoms of dysphagia, · oesophageal varices, stricture or requiring dilatation of the oesophagus · on anticoagulation therapy/medication (warfarin, clopridogrel,heparin or tinzaparin). · Individuals who have had a myocardial infarction or any cardiac event less than six months ago. · Individuals who have had a cerebrovascular event Principal Investigator for this trial: Dr Krish Ragunath

Research Ethics Committee Reference: 10/H0308/71

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Oesophageal Cancer Clinical and Molecular Stratification Study – OCCAMS – A prospective Multicentre Trial of a revised clinical and molecular staging system for Oesophageal and Junctional Adenocarcinoma

Summary:
Cancers that occur at the junction between the oesophagus (gullet) and the stomach are called gastro oesophageal junction (GOJ) adenocarcinomas. They are 6 times more common than they were 30 years ago and have a very poor outcome (only 1 in 5 patients will survive five years). We have previously developed a new way of determining how advanced a patient’s GOJ adenocarcinoma is (what we call staging) using both the physical features determined by the radiology tests and the molecular features of the cancer. This system works significantly better than the existing way we stage these cancers. However this new system was developed using patients who had already had their surgery. We now want to test it on patients at the beginning of their treatment or what we term prospectively. The patients management will not differ from current practice but as well as looking at the features used for staging at the moment we will also record our new system in parallel. We will also test samples of the cancer, which are already routinely taken, for the molecular changes we think will predict survival. After this patients will undergo the standard treatment at each of the centres involved. It will then be possible to determine both how practical our new system is and how good it is at predicting survival. We will be running this prospective trial in multiple hospitals across the country to ensure that our system is broadly applicable. If we can prove that our revised staging system, using both the physical features of the tumour and the molecular changes, can accurately predict outcome this will allow us to give far better information to our patients about their chance of a cure but also it will also allow treatments to be targeted at those who will benefit the most.

Inclusion criteria:
The inclusion criteria is any patient with tissue proven diagnosis of adenocarcinoma (distal oesophageal, and Siewert types I, II and III) being treated with curative intent (oesophagectomy or extended total gastrectomy). The exclusion criteria are patients undergoing palliative treatment and those unable or unwilling to consent.

Principal Investigator for this trial: Mr Simon Leslie Parsons

Research Ethics Committee Reference: 10/H0305/1

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Oesophageal Cancer Clinical and Molecular Stratification Study – OCCAMS – A prospective Multicentre Trial of a revised clinical and molecular staging system for Oesophageal and Junctional Adenocarcinoma

Summary:
Cancers that occur at the junction between the oesophagus (gullet) and the stomach are called gastro oesophageal junction (GOJ) adenocarcinomas. They are 6 times more common than they were 30 years ago and have a very poor outcome (only 1 in 5 patients will survive five years). We have previously developed a new way of determining how advanced a patient’s GOJ adenocarcinoma is (what we call staging) using both the physical features determined by the radiology tests and the molecular features of the cancer. This system works significantly better than the existing way we stage these cancers. However this new system was developed using patients who had already had their surgery. We now want to test it on patients at the beginning of their treatment or what we term prospectively. The patients management will not differ from current practice but as well as looking at the features used for staging at the moment we will also record our new system in parallel. We will also test samples of the cancer, which are already routinely taken, for the molecular changes we think will predict survival. After this patients will undergo the standard treatment at each of the centres involved. It will then be possible to determine both how practical our new system is and how good it is at predicting survival. We will be running this prospective trial in multiple hospitals across the country to ensure that our system is broadly applicable. If we can prove that our revised staging system, using both the physical features of the tumour and the molecular changes, can accurately predict outcome this will allow us to give far better information to our patients about their chance of a cure but also it will also allow treatments to be targeted at those who will benefit the most.

Inclusion criteria:
The inclusion criteria is any patient with tissue proven diagnosis of adenocarcinoma (distal oesophageal, and Siewert types I, II and III) being treated with curative intent (oesophagectomy or extended total gastrectomy). The exclusion criteria are patients undergoing palliative treatment and those unable or unwilling to consent.

Principal Investigator for this trial: Mr Simon Leslie Parsons

Research Ethics Committee Reference: 10/H0305/1

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

ACCEPT – A phase Ib/II combination trial of acalabrutinib with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (R-CHOP) (for patients with Diffuse Large B-Cell lymphoma)

Summary:
Diffuse large B-cell lymphoma (DLCBL) is the commonest of the non-Hodgkin’s lymphomas. Whilst the majority of
patients will respond well to conventional immunochemotherapy (R-CHOP), a significant number of patients will either
fail to respond to initial therapy or relapse after completion of therapy. Bruton’s tyrosine kinase (BTK) is an enzyme
dysregulated in numerous B-cell malignancies, including DLCBL. Acalabrutinib is an orally active BTK-inhibitor. It is
hypothesised that the addition of acalabrutinib to standard R-CHOP immunochemotherapy may improve outcomes of
patients with DLCBL.
The proposed study is a phase Ib/II clinical trial to determine a suitable tolerated dose and efficacy of acalabrutinib in
combination with standard R-CHOP immunochemotherapy to treat patients with DLBCL.
The main aims of this clinical study are to find out:
-The maximum dose of acalabrutinib that can safely be given to patients
-More about the potential side effects of acalabrutinib and how they can be managed
-The effect the combination of R-CHOP and acalabrutinib has on DLBCL
Approximately 6-24 patients with DLBCL will be entered into the dose-escalation phase, and a further 15 patients will
be recruited to a dose expansion cohort. The final number will depend on the number of dose escalations required.

Inclusion criteria:
1. Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to a
central laboratory for gene expression profiling and pathology review
2. Measurable disease of at least 15mm
3. Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative
intent
4. Stage IAX (bulk defined as lymph node diameter >10cm) to stage IV disease and deemed to require a full course of
chemotherapy. Patients with non-bulky IE disease are not eligible
5. ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma
6. Adequate bone marrow function with platelets > 100×109/L; neutrophils > 1.0×109/L at study entry, unless lower
figures are attributable to lymphoma
7. Measured or calculated creatinine clearance > 30mls/min, (calculated using the formula of Cockcroft and Gault
[(140-Age) x Mass (kg)x(1.04 (for women)or 1.23 (for men))/Serum Creatinine (umolL)]
8. Serum bilirubin 3 months
12. Aged 16 years or above
13. Willing and able to participate in all required evaluations and procedures in this study protocol including
swallowing capsules without difficulty
14. Ability to understand the purpose and risks of the study and provide signed and dated informed consent

Exclusion criteria:
1. Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are
found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be
eligible
2. Diagnosis of primary mediastinal lymphoma
3. Diagnosis of primary Central Nervous System lymphoma.
4. History of stroke or intracranial haemorrhage in preceding 6 months
5. History of bleeding diathesis (eg. haemophilia, von Willebrand disease)
6. Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg. phenprocoumon) within 7 days of
first dose of acalabrutinib. However patients using therapeutic low molecule weight heparin or low dose aspirin will be
eligible
7. Prior exposure to a BCR inhibitor(eg. BtK inhibitors, phosphoinositide-3 kinase (PI3K), or SyK inhibitors) or BCL-2
inhibitor (eg. ABT-199)
8. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
9. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole,
rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to short-acting H2-receptor
antagonists or antacids are eligible for enrolment into this study.
10. Uncontrolled systemic infection
11. Major surgery in the preceding 4 weeks of first dose of study drug. If a subject had major surgery, they must have
recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug
12. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or
myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York
Heart Association Functional Classification, or corrected QT interval (QTc) > 480 msec at screening.
13. Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of
immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
– Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients
with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients
who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
– Positive test results for hepatitis C virus (HCV) antibody serology will not be eligible.
14. Women who are sexually active and can bear children must agree to use highly effective forms of contraception
during the study and for 90 days after the last dose of acalabrutinib. Highly effective forms of contraception are
defined in Section 4.7
14. Breastfeeding or pregnant
15. Men who are sexually active and can potentially father children must agree to use highly effective forms of
contraception during the study and for 90 days after the last dose of acalabrutinib. Highly effective forms of
contraception are defined in Section 4.7
16. Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of study drug.
17. Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give
informed consent
18. Prior malignancy (other than DLBCL), except for adequately treated basal cell or squamous cell skin cancer, in situ
cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit
survival to Principal Investigator for this trial: Dr Andrew McMillan

Research Ethics Committee Reference: 16/SC/0657

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

The cystic fibrosis (CF) anti-staphylococcal antibiotic prophylaxis trial (CF START); a randomised registry trial to assess the safety and efficacy of flucloxacillin as a longterm prophylaxis agent for infants with CF

Summary:
CF START is a national UK trial that will determine the safest and most effective antibiotic strategy for infants
diagnosed with cystic fibrosis (CF). 480 CF infants will be randomly allocated either flucloxacillin prophylaxis (the
current UK standard of care) or antibiotics given in a more targeted manner. The primary outcome will be the age at
first growth of Pseudomonas aeruginosa from a respiratory culture (an important safety measure for families). All
outcomes will be recorded on a national CF Registry, including a number of secondary outcomes assessing
effectiveness and safety. Finally at 40-48 months, a measure of respiratory function will be undertaken in a central
laboratory, which will provide a clearer indication of the effectiveness of these two strategies.

Inclusion criteria:
1. A confirmed diagnosis of cystic fibrosis through one of the following three routes:
– Two CF-causing mutations are identified.
OR
– One or no CF- causing mutations identified and a sweat chloride test result greater than 59 mmol/L.
OR
– Two CFTR mutations (not known CF-causing mutations) and a sweat chloride test result greater than 29 mmol/L.
2. Age 70 days or less.
3. Consent for inclusion on the national UK CF Registry.
4. Consent for inclusion in the CF START trial.

Exclusion criteria:
1. An inconclusive diagnosis after newborn screening (NBS).*
2. A condition (non-CF) that, in the opinion of the recruiting investigator will impact on the long-term management and
outcome of a participant with CF.**
3. Previous growth of PsA from respiratory culture.
4. Infants with a history of hypersensitivity to β-lactam antibiotics (e.g. penicillins) or excipients
5. Infants with a history of flucloxacillin associated jaundice/hepatic dysfunction.
*Infants with an inconclusive diagnosis after NBS (termed ‘CF Screen Positive Inconclusive Diagnosis (CFSPID)’)
should not receive standard CF care and should not be recruited into CF START (Munck et al 2015).
The two situations that result in a diagnosis of CFSPID after NBS are;
• Two CFTR mutations recognised, one or both of which are not characterised as CF-causing and the sweat chloride
is less than 30 mmol/L
• The sweat chloride is repeatedly between 30-59 mmol/L and only one or no CFTR mutations are recognised
**Significant non-CF conditions might include chromosomal abnormality (for example, Down syndrome), cerebral
palsy, chronic lung disease (oxygen requirement) following pre-term birth and other significant congenital anomalies
(for example, severe cardiac disease, tracheo-oesophageal fistula, diaphragmatic hernia).

Principal Investigator for this trial: Professor Alan Smyth

Research Ethics Committee Reference: 16/NW/0629

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Albumin To prevenT Infection in chronic liveR failurE (ATTIRE)

Summary:
Liver disease is the fifth most common cause of death in the UK and is caused largely by alcohol, viruses and fatty liver disease resulting in liver damage and loss of function. People can survive with large amounts of liver damage but often have severe health complications leading to frequent hospital admissions. In particular, patents have weak immune systems and are highly prone to bacterial infection with over a third developing an infection in hospital. Infection is the major cause of death in these patients and therefore represents a huge challenge to the NHS.

Currently infection in liver patients is treated with antibiotics, however the rates of death in these patients have shown little improvement over 20 years. Antibiotics may also cause harmful side-effects (e.g. diarrhoea) and overuse has led to antibiotic resistant bacteria which makes these drugs useless and will be one of medicines’ greatest challenges over the next decade.

Our study aims to see if giving liver patients Human Albumin Solution restores their immune response and helps both prevent and improve treatment of infections. Albumin is a protein found naturally in blood and is made in the liver. As liver function reduces so does albumin production and blood levels fall. Albumin is safe and currently used in patients with liver failure; however, prescription is varied and although considered beneficial the effects haven’t been tested in clinical trials.

This study includes a feasibility study, to verify whether it is possible to restore albumin levels to near normal. This will be followed by a randomised control trial to confirm whether restoring albumin levels improves survival from infection compared to standard treatment.

The study will take place at up to 40 NHS sites in England, Wales and Scotland involving 946 patients and is supported by the Department of Health and the Wellcome Trust.

Inclusion criteria:
• All patients admitted to hospital with acute onset or worsening of complications of cirrhosis e.g. alcoholic hepatitis, hepatic encephalopathy, ascites, hepatic hydrothorax, hyperbilirubinaemia, oesophageal variceal bleed, any infection precipitating acute decompensation or any other presentation of acute decompensation / acute onset chronic liver failure
• Over 18 years of age
• Predicted hospital admission > 5 days at trial enrolment, which must be within 72 hours of admission
• Serum albumin Exclusion criteria:
• Advanced hepatocellular carcinoma with life expectancy of less than 8 weeks
• Patients who will receive palliative treatment only during their hospital admission
• Patients who are pregnant
• Severe cardiac dysfunction
• Any clinical condition which the investigator considers would make the patient unsuitable for the trial
• The patient has been involved in a clinical trial of Investigational Medicinal Products (IMPs) within the previous 30 days (including re-randomisation into the RCT)
• Trial investigators unable to identify the patient (by NHS number)

Principal Investigator for this trial: Dr Stephen D Ryder

Research Ethics Committee Reference: 15/LO/0104

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A randomised doubleblind controlled phase III study to compare the efficacy and safety of intravenous ferric carboxymaltose with placebo in patients with anaemia undergoing major open abdominal surgery

Summary:
Anaemia is a common problem in patients undergoing surgery. About half of patients undergoing a major operation have anaemia, often a consequence of the disease requiring surgery. Anaemia causes patients to feel tired and unwell. Anaemia at t… Continue reading

Digital Health Records

The Digital Health Records (Unity) system is designed, built and tested to meet information governance and data protection requirements.
All NUH staff accessing DHR Unity must adhere to NUH Trust policies in relation to patient confidentiality and data protection.
The DHR … Continue reading

A prospective, multicenter, randomised, open-label, active controlled, two-parallel groups, phase 3 study to compare the efficacy and safety of masitinib to sunitinib in patients with gastrointestinal stromal tumor after progression with imatinib at 400mg as first line treatment.

Summary:
Gastrointestinal stromal tumors (GIST) are uncommon visceral sarcomas that arise in the stomach (60-70%), small intestine (20-30%), colon and rectum (5%) and oesophagus (Inclusion criteria:
1. Patient with histological proven non-operable locally advanced or metastatic Gastro Intestinal Stromal Tumour (GIST)
2. Patient with measurable tumor lesions with longest diameter ≥(greater than or equal to) 20 mm using conventional techniques or ≥ 10 mm with spiral CT scan according RECIST criteria
3. Patient with Ckit (CD117) positive tumour detected immuno-histochemically
4. Patients after progression with imatinib at the dose of 400 mg/day as first line of treatment. Progression is defined as a RECIST 1.1 disease progression under imatinib treatment
5. Patient with ECOG ≤(less than or equal to) 2
6. Patient with adequate organ functions:
• Absolute neutrophils count (ANC) ≥ 1.5 x 109/L
• Haemoglobin ≥ 10 g/dL
• Platelets (PTL) ≥ 75 x 109/L
• AST/ALT ≤ 2.5x ULN (≤ 5 x ULN in case of liver metastases)
• Gamma GT 1 x LLN
• Urea ≤ 2 x ULN
• Proteinuria 6 months
8. Male or female patient, age >18 years
9. Patient with a BMI > 18 kg/m² and weighing at least 40kg
10. Male and female patient of child bearing potential, (for female entering the study after a menstrual period and who have a negative pregnancy test at baseline) must agree to use two effective methods of contraception, one highly effective and one additionally effective or to practice abstinence from heterosexual contact during the study and for 3 months after the last treatment intake.
The following are examples of highly effective and additional effective methods of contraception:
Highly effective methods:
– Intrauterine device (IUD)
– Hormonal (birth control pills, injections, implants)
– Tubal ligation
– Partner’s vasectomy
Additional effective methods:
– Male condom
– Diaphragm
– Cervical Cap
This protocol defines a female of childbearing potential as a sexually mature woman who has not undergone a
hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal (amenorrhea following cancer
therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
11. Patient able and willing to comply with study procedures as per protocol
12. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures
13. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment
14. Patient affiliated to a social security regimen (for France only) and/or covered by insurance reimbursing sunitinib

Exclusion criteria:
1. Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell
carcinoma or cervical cancer in situ.
2. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
3. Patient presenting with cardiac disorders defined by at least one of the following conditions:
• Patient with recent cardiac history (within 6 months) of:
– Acute coronary syndrome
– Acute heart failure (class III or IV of the NYHA classification)
– Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
• Patient with cardiac failure class III or IV of the NYHA classification
• Patient with severe conduction disorders which are not prevented by permanent pacing (atrioventricular
block 2 and 3, sinoatrial block)
• Syncope without known aetiology within 3 months
• Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
4. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
5. Pregnant, or nursing female patient
• Previous treatment
6. Known hypersensitivity to sunitinib or masitinib or to any of the exicipients
7. Patient previously treated with a dose of imatinib > 400mg
8. Patient intolerant to imatinib
9. Previous treatment with sunitinib or kinase inhibitor other than imatinib
• Washout
10. Treatment with any investigational agent within 4 weeks prior to baseline
11. Previous imatinib treatment should be permanently discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib

Principal Investigator for this trial: Dr Ivo Hennig

Research Ethics Committee Reference: 13/WS/0228

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients with Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses

Summary:
An experimental drug called ponatinib is being studied as a possible cancer treatment for participants with chronic
myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are no longer benefitting from their current treatment.
The purpose of the trial is to evaluate different starting doses (strengths) of ponatinib to determine which dose
provides the best control of disease and the least amount of side effects.
Participants will be randomly assigned to receive one of three starting doses of ponatinib, which means being
assigned by chance, like the flip of a coin.
Participants and the Study Doctor will know which ponatinib dose they are receiving.
Duration of participation will be 24 months. Screening tests will be performed for up to 3 weeks prior to treatment to determine if participants meet the criteria to take part in this trial. The length of time participants will take ponatinib will depend on cancer status (if there is benefit from treatment) and how well ponatinib is tolerated.

Inclusion criteria:
1. Have CP-CML and are resistant to at least two prior TKIs.
a. The diagnosis of CML will be made using standard hematopathologic and cytogenetic criteria. CP-CML
will be defined by all of the following:
i 95% Ph+) or failure to achieve CHR
ii Six months after the initiation of prior TKI therapy: Less than a minor cytogenetic response (> 65% Ph+)
iii Twelve months after the initiation of prior TKI therapy: Less than a PCyR (> 35% Ph+)
iv At any time after the initiation of prior TKI therapy, the development of new BCR-ABL kinase domain mutations in the absence of MCyR
v At any time after the initiation of prior TKI therapy, the development of new clonal evolution in the absence of MCyR
vi At any time after the initiation of prior TKI therapy, the loss of any cytogenetic response (from complete [0%] or partial [1% to 35%] to anything less than a partial response; or from minor [36% to 65%], or minimal [66% to 95%] to a response at least 1 grade worse), confirmed in at least 2 consecutive analyses separated by at least 4 weeks
2. Be male or female patients ≥ 18 years old.
3. Have an ECOG performance status of 0, 1, or 2.
4. Have adequate renal function as defined by the following criterion:
a. Serum creatinine ≤ 1.5 × ULN for institution
5. Have adequate hepatic function as defined by the following criteria:
a. Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert’s syndrome
b. ALT ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic involvement of the liver is present
c. AST ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic involvement of the liver is present
6. Have normal pancreatic status as defined by the following criterion:
a. Serum lipase and amylase ≤ 1.5 × ULN
7. Have normal QTcF interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in
males or ≤ 470 ms in females.
8. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
9. Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile).
10. Provide written informed consent.
11. Be willing and able to comply with scheduled visits and study procedures.
12. Have fully recovered (≤ grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug.

Exclusion criteria:
1. Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
2. Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by NCI CTCAE, v4.0) from AEs (except alopecia), due to agents previously administered.
3. Have undergone autologous or allogeneic SCT 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
11. Have poorly controlled diabetes, defined as HbA1c values over the previous year of > 7.5% (59 mmol/mol) on more than 3 occasions; patients with pre-existing,
well-controlled, diabetes are not excluded.
12. Have a significant bleeding disorder unrelated to CML.
13. Have a history of alcohol abuse.
14. Have a history of either acute pancreatitis within 1 year of study or of chronic pancreatitis.
15. Have malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption of study drug.
16. Have a history of another malignancy, other than cervical cancer in situ or nonmetastatic basal cell or squamous cell carcinoma of the skin; the exception is if patients have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
17. Are pregnant or lactating.
18. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement) within 14 days prior to first dose of ponatinib.
19. Have an ongoing or active infection; this includes, but is not limited to, the requirement for intravenous antibiotics.
20. Have a known history of human immunodeficiency infection; testing is not required in the absence of prior documentation or known history.
21. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the drug.

Principal Investigator for this trial: Dr Jennifer Byrne

Research Ethics Committee Reference: 15/LO/1192

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients with Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses

Summary:
An experimental drug called ponatinib is being studied as a possible cancer treatment for participants with chronic
myeloid leukaemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL) who are no longer benefitting from their current treatment.
The purpose of the trial is to evaluate different starting doses (strengths) of ponatinib to determine which dose
provides the best control of disease and the least amount of side effects.
Participants will be randomly assigned to receive one of three starting doses of ponatinib, which means being
assigned by chance, like the flip of a coin.
Participants and the Study Doctor will know which ponatinib dose they are receiving.
Duration of participation will be 24 months. Screening tests will be performed for up to 3 weeks prior to treatment to determine if participants meet the criteria to take part in this trial. The length of time participants will take ponatinib will depend on cancer status (if there is benefit from treatment) and how well ponatinib is tolerated.

Inclusion criteria:
1. Have CP-CML and are resistant to at least two prior TKIs.
a. The diagnosis of CML will be made using standard hematopathologic and cytogenetic criteria. CP-CML
will be defined by all of the following:
i 95% Ph+) or failure to achieve CHR
ii Six months after the initiation of prior TKI therapy: Less than a minor cytogenetic response (> 65% Ph+)
iii Twelve months after the initiation of prior TKI therapy: Less than a PCyR (> 35% Ph+)
iv At any time after the initiation of prior TKI therapy, the development of new BCR-ABL kinase domain mutations in the absence of MCyR
v At any time after the initiation of prior TKI therapy, the development of new clonal evolution in the absence of MCyR
vi At any time after the initiation of prior TKI therapy, the loss of any cytogenetic response (from complete [0%] or partial [1% to 35%] to anything less than a partial response; or from minor [36% to 65%], or minimal [66% to 95%] to a response at least 1 grade worse), confirmed in at least 2 consecutive analyses separated by at least 4 weeks
2. Be male or female patients ≥ 18 years old.
3. Have an ECOG performance status of 0, 1, or 2.
4. Have adequate renal function as defined by the following criterion:
a. Serum creatinine ≤ 1.5 × ULN for institution
5. Have adequate hepatic function as defined by the following criteria:
a. Total serum bilirubin ≤ 1.5 × ULN, unless due to Gilbert’s syndrome
b. ALT ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic involvement of the liver is present
c. AST ≤ 2.5 × ULN, or ≤ 5 × ULN if leukemic involvement of the liver is present
6. Have normal pancreatic status as defined by the following criterion:
a. Serum lipase and amylase ≤ 1.5 × ULN
7. Have normal QTcF interval on screening ECG evaluation, defined as QTcF of ≤ 450 ms in
males or ≤ 470 ms in females.
8. Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).
9. Agree to use an effective form of contraception with sexual partners throughout study participation (for female and male patients who are fertile).
10. Provide written informed consent.
11. Be willing and able to comply with scheduled visits and study procedures.
12. Have fully recovered (≤ grade 1, returned to baseline, or deemed irreversible) from the acute effects of prior cancer therapy before initiation of study drug.

Exclusion criteria:
1. Have used any approved TKIs or investigational agents within 2 weeks or 6 half-lives of the agent, whichever is longer, prior to receiving study drug.
2. Received interferon, cytarabine, or immunotherapy within 14 days, or any other cytotoxic chemotherapy, radiotherapy, or investigational therapy within 28 days prior to receiving the first dose of ponatinib, or have not recovered (> grade 1 by NCI CTCAE, v4.0) from AEs (except alopecia), due to agents previously administered.
3. Have undergone autologous or allogeneic SCT 90 mmHg; systolic > 150 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
11. Have poorly controlled diabetes, defined as HbA1c values over the previous year of > 7.5% (59 mmol/mol) on more than 3 occasions; patients with pre-existing,
well-controlled, diabetes are not excluded.
12. Have a significant bleeding disorder unrelated to CML.
13. Have a history of alcohol abuse.
14. Have a history of either acute pancreatitis within 1 year of study or of chronic pancreatitis.
15. Have malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption of study drug.
16. Have a history of another malignancy, other than cervical cancer in situ or nonmetastatic basal cell or squamous cell carcinoma of the skin; the exception is if patients have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
17. Are pregnant or lactating.
18. Have undergone major surgery (with the exception of minor surgical procedures, such as catheter placement) within 14 days prior to first dose of ponatinib.
19. Have an ongoing or active infection; this includes, but is not limited to, the requirement for intravenous antibiotics.
20. Have a known history of human immunodeficiency infection; testing is not required in the absence of prior documentation or known history.
21. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the drug.

Principal Investigator for this trial: Dr Jennifer Byrne

Research Ethics Committee Reference: 15/LO/1192

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase III doubleblind placebocontrolled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumours.

Summary:
Add-Aspirin is a large clinical trial for people who have had treatment for breast, colorectal, gastro-oesophageal
or prostate cancer. The aim of the trial is to find out whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back.
Participants will self-administer 100mg aspirin once daily for 8 weeks. After 8 weeks, if taking regular aspirin does not cause any serious problems, participants will be randomly allocated to self-administer either a 300mg aspirin tablet, a 100mg aspirin tablet or a placebo tablet once daily for at least five years. Participants who are 75 years old or over, will only be allocated to 100mg aspirin tablets daily or placebo tablets. To ensure the results of the trial are as reliable as possible, neither the participants, nor the clinicians will know which tablets participants are allocated to.
In total, 9,920 participants will be randomised into the trial over 3 – 6 years (depending on tumour site). All participants will be followed-up within the trial for at least 5 years. In the UK, long-term follow-up data will also be obtained from routinely-collected healthcare databases.
A programme of associated correlative science is planned incorporating both short and long-term projects which will
investigate key questions including: determining the mechanism of action for an anti-cancer effect of aspirin;
determining biomarkers that identify participants most likely to experience serious aspirin-related toxicity; determining the roles of genotypic and phenotypic differences in aspirin’s actions; identifying individuals who will benefit most or least from aspirin and determining the mechanisms underlying potential non-cancer benefits of aspirin.

Inclusion criteria:
COMMON INCLUSION CRITERIA
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease
BREAST COHORT INCLUSION CRITERIA
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
a. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further
intervention) should be completed prior to registration
b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT)
a. Patients who have undergone breastconserving
surgery should receive adjuvant RT
b. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
c. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not)
receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
a. Node positive
b. Node negative with high-risk features -2 or more of:
i. ER negative
ii. HER2 positive
iii. Grade 3
iv. Lymphovascular invasion present
v. Age 25
c. In patients who have received neo-adjuvant
chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant
and/or adjuvant chemotherapy or RT are eligible.
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy
COLORECTAL COHORT INCLUSION CRITERIA
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone
resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally ≤1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins
GASTRO-OESOPHAGEAL
COHORT INCLUSION CRITERIA
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the
oesophagus, gastro-oesophageal
junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent
PROSTATE COHORT INCLUSION CRITERIA
1. Men with histologically confirmed node negative non-metastatic adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
a. Radical prostatectomy
b. Radical RT
c. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
(a) Prostatectomy patients
4. Open, laparoscopic or robotic radical prostatectomy
5. Men treated with immediate adjuvant RT
6. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
7. Men randomised to any of the 3 arms of RADICALS HD are eligible
(b) Radical RT patients
9. Men receiving neo-adjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3yrs
(c) Salvage RT patients following PSA rise after previous radical prostatectomy
13. Men treated with salvage RT following a rise in PSA are eligible
14. Men receiving neo-and/ or adjuvant hormone therapy planned for a maximum of 3yrs
15. Men randomised to any of the 3 arms of RADICALS HD are eligible

Exclusion criteria:
COMMON EXCLUSION CRITERIA
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or
sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
3. Current use of anti-coagulants.
4. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term
therapy.
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of
bleeding has been surgically removed.
7. Active or previous history of inflammatory bowel disease.
8. History of moderate or severe renal impairment, with eGFR3 years.
3. Bilateral orchidectomy.

Principal Investigator for this trial: Dr Georgina Walker

Research Ethics Committee Reference: 14/SC/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A phase III doubleblind placebocontrolled randomised trial assessing the effects of aspirin on disease recurrence and survival after primary therapy in common nonmetastatic solid tumours.

Summary:
Add-Aspirin is a large clinical trial for people who have had treatment for breast, colorectal, gastro-oesophageal
or prostate cancer. The aim of the trial is to find out whether taking aspirin regularly after treatment for early stage cancer stops or delays the cancer coming back.
Participants will self-administer 100mg aspirin once daily for 8 weeks. After 8 weeks, if taking regular aspirin does not cause any serious problems, participants will be randomly allocated to self-administer either a 300mg aspirin tablet, a 100mg aspirin tablet or a placebo tablet once daily for at least five years. Participants who are 75 years old or over, will only be allocated to 100mg aspirin tablets daily or placebo tablets. To ensure the results of the trial are as reliable as possible, neither the participants, nor the clinicians will know which tablets participants are allocated to.
In total, 9,920 participants will be randomised into the trial over 3 – 6 years (depending on tumour site). All participants will be followed-up within the trial for at least 5 years. In the UK, long-term follow-up data will also be obtained from routinely-collected healthcare databases.
A programme of associated correlative science is planned incorporating both short and long-term projects which will
investigate key questions including: determining the mechanism of action for an anti-cancer effect of aspirin;
determining biomarkers that identify participants most likely to experience serious aspirin-related toxicity; determining the roles of genotypic and phenotypic differences in aspirin’s actions; identifying individuals who will benefit most or least from aspirin and determining the mechanisms underlying potential non-cancer benefits of aspirin.

Inclusion criteria:
COMMON INCLUSION CRITERIA
1. Written informed consent
2. WHO performance status 0, 1 or 2
3. Previous or current participants of other primary treatment trials if agreed in advance between trials
4. No clinical or radiological evidence of residual or distant disease
BREAST COHORT INCLUSION CRITERIA
1. Men or women with histologically confirmed invasive breast cancer
2. Undergone complete primary invasive tumour excision with clear margins
3. Surgical staging of the axilla must have been undertaken by sentinel node biopsy, axillary sampling or dissection
4. In those patients with a positive sentinel node biopsy:
a. If 1, 2 or 3 nodes are positive, subsequent management of the axilla (with surgery, radiotherapy or no further
intervention) should be completed prior to registration
b. If 4 or more nodes are involved, patients must have undergone completion axillary node dissection
5. Radiotherapy (RT)
a. Patients who have undergone breastconserving
surgery should receive adjuvant RT
b. Patients who have undergone mastectomy should receive RT if they have more than 3 axillary lymph nodes involved
c. Patients who have undergone mastectomy and have T3 tumours and/or 1, 2 or 3 involved lymph nodes may (or not)
receive radiation per institutional practice
6. Final histology must fall within at least one of these 3 groups:
a. Node positive
b. Node negative with high-risk features -2 or more of:
i. ER negative
ii. HER2 positive
iii. Grade 3
iv. Lymphovascular invasion present
v. Age 25
c. In patients who have received neo-adjuvant
chemotherapy, patients are eligible if they have both a hormone receptor negative/HER2 negative tumour, a HER2 positive tumour or a hormone receptor positive grade 3 tumour and did not achieve a pathological complete response with neoadjuvant systemic therapy
7. Patients who received standard neoadjuvant
and/or adjuvant chemotherapy or RT are eligible.
8. Known HER2 and ER status
9. Participants may receive endocrine therapy and trastuzumab. All ER positive patients should be planned to undergo at least 5 yrs of adjuvant endocrine therapy
COLORECTAL COHORT INCLUSION CRITERIA
1. Histologically confirmed stage II or III adenocarcinoma of the colon or rectum and patients who have undergone
resection of liver metastases with clear margins and no residual metastatic disease
2. Patients with synchronous tumours if one of the tumours is at least stage II or III
3. Serum CEA ideally ≤1.5 x upper limit of normal
4. Have undergone curative (R0) resection with clear margins
GASTRO-OESOPHAGEAL
COHORT INCLUSION CRITERIA
1. Patients with histologically confirmed adenocarcinoma, adenosquamous carcinoma or squamous cell cancer of the
oesophagus, gastro-oesophageal
junction or stomach
2. Have undergone curative (R0) resection with clear margins or primary chemoRT given with curative intent
PROSTATE COHORT INCLUSION CRITERIA
1. Men with histologically confirmed node negative non-metastatic adenocarcinoma of the prostate
2. Have undergone curative treatment, either:
a. Radical prostatectomy
b. Radical RT
c. Salvage RT (following rise in PSA after prostatectomy)
3. Intermediate or high risk according to D’Amico classification

Treatment pathway specific inclusion criteria:
(a) Prostatectomy patients
4. Open, laparoscopic or robotic radical prostatectomy
5. Men treated with immediate adjuvant RT
6. Men receiving adjuvant hormone therapy planned for a maximum duration of 3 yrs
7. Men randomised to any of the 3 arms of RADICALS HD are eligible
(b) Radical RT patients
9. Men receiving neo-adjuvant and/or adjuvant hormone therapy planned for a maximum duration of 3yrs
(c) Salvage RT patients following PSA rise after previous radical prostatectomy
13. Men treated with salvage RT following a rise in PSA are eligible
14. Men receiving neo-and/ or adjuvant hormone therapy planned for a maximum of 3yrs
15. Men randomised to any of the 3 arms of RADICALS HD are eligible

Exclusion criteria:
COMMON EXCLUSION CRITERIA
1. Current or previous regular use of aspirin (at any dose) or current use of another NSAID for any indication.
2. A past history of adverse reaction or hypersensitivity to NSAIDs, celecoxib, aspirin or other salicylates or
sulphonamides, including asthma, that is exacerbated by use of NSAIDs.
3. Current use of anti-coagulants.
4. Current or long-term use of oral corticosteroids. The treating physician should make the clinical decision whether a patient has been exposed to long-term
therapy.
5. Active or previous peptic ulceration or gastrointestinal bleeding within the last year, except where the cause of
bleeding has been surgically removed.
7. Active or previous history of inflammatory bowel disease.
8. History of moderate or severe renal impairment, with eGFR3 years.
3. Bilateral orchidectomy.

Principal Investigator for this trial: Dr Georgina Walker

Research Ethics Committee Reference: 14/SC/0171

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase 3 Study of ACP-196 Versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia

Summary:
Chronic Lymphocytic Leukaemia (CLL) is a cancer of B cells (a type of white blood cell) that predominantly affects the elderly population.
Chemoimmunotherapy has become a standard for the treatment of young and/or fit individuals with CLL who require treatment. However, elderly subjects and those with pre exisiting diseases are often unable to tolerate combination chemoimmunotherapy regimens, or experience inferior outcomes. Ibrutinib, a type of orally administered drug called a Btk inhibitor, was recently approved for certain groups of patients with CLL and has shown favourable outcomes for these patients. ACP-196 has recently been identified and is also an orally administered Btk inhibitor but inhibits more selectively than Ibrubtinib ACP-196 has been well tolerated in healthy volunteers and patients with CLL and has shown sustained improvement in symptoms of CLL.
This study, sponsored by Acerta Pharma, will investigate if ACP-196 is as effective as Inbrutinib and if it is safe. 500 patients over the age of 18 will take part over 100 sites globally with approximately 7 hospitals in the UK. Half the patients will receive Inbrutinib and half will receive ACP-196. Patients will be randomised (by chance) to the study treatment and will know which treatment they are receiving.
Each patient will give informed consent and will be screened for suitability and will be in the study for approximately 4 years unless early withdrawal is necessary. Patients will visit their study doctor every week for 9 weeks and then every 12 weeks and will undergo tests per the schedule in the study protocol such as physical examinations, vital signs, complete diaries and questionaires, blood tests for safety and effectiveness of study drugs, CT scans and ECG.

Inclusion criteria:
Key Inclusion Criteria are:
Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
o Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 Bcell marker (CD19, CD20, or CD23) and CD5.
o Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
o No evidence of cyclin D1 rearrangement or BCL-1
over expression.
• Must have ≥ 1 of the following high-risk prognostic factors:
o Presence of 17p del by central laboratory
o Presence of 11q del by central laboratory
• Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:
o Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin 50% over a 2-month period or a lymphocyte doubling time (LDT) of 1 month before Screening without evidence of infection.
• Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as ≥ 1 lymph node > 1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may
be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
• Must have received ≥ 1 prior therapies for CLL.
• Meet the following laboratory parameters:
o Absolute neutrophil count (ANC) ≥ 750 cells/μL (0.75 x 109/L) or ≥ 500 cells/μL (0.50 x 109/L) in subjects with
documented bone marrow involvement and independent of growth factor support 7 days before assessment.
o Platelet count ≥ 30,000 cells/μL (30 x 109/L) without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
o Serum aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) 45 years of age and without menses for > 1 year) and surgically sterilized women are exempt from this criterion.
• Men must agree to use acceptable methods of contraception during the study and for 30 days after the last dose of ACP-196 or ibrutinib if sexually active with a woman of childbearing potential.
• Men must agree to refrain from sperm donation during the study and for 30 days after the last dose of ACP-196
or ibrutinib.
• Are willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorisation to use protected health information. Note vulnerable subjects are not allowed on this protocol (eg, prisoners or institutionalised participants).

Exclusion criteria:
Key Exclusion Criteria are:
Known central nervous system (CNS) lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome.
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to
autoimmune destruction within the screening period or
requirement for high doses of steroids (> 20 mg daily of
prednisone daily or equivalent).
• Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor (eg, Bruton tyrosine kinase [Btk] inhibitors or phosphoinositide-3 [PI3] kinase inhibitors or Syk inhibitors) or a BCL-2 inhibitor (eg, ABT199).
• Received any chemotherapy, external beam radiation
therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
• Corticosteroid use > 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded.
• Prior radio-or toxin-conjugated antibody therapy.
• Prior allogeneic stem cell transplant or autologous transplant.
• Major surgery within 4 weeks before first dose of study drug.
• History of prior malignancy except for the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician
o Adequately treated lentigo maligna melanoma without
current evidence of disease or adequately controlled
non-melanomatous skin cancer
o Adequately treated cervical carcinoma in situ without
current evidence of disease
• Currently active clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months before first dose with study drug.
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment.
• Known history of infection with human immunodeficiency virus (HIV).
• Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.
• History of stroke or intracranial hemorrhage within 6 months before randomization.
• History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
• Requires or receiving anticoagulation with warfarin or
equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
• Requires treatment with a strong cytochrome P450 3A4
(CYP3A4) inhibitor/inducer.
• Requires treatment with longacting proton pump inhibitors(eg,omeprazole,esomeprazole, lansoprazole,dexlansoprazole, rabeprazole, or pantoprazole)Breast feeding or pregnant.
• Concurrent participation in another therapeutic clinical trial.

Principal Investigator for this trial: Dr Christopher P Fox

Research Ethics Committee Reference: 15/NW/0492

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase 3 Study of ACP-196 Versus Ibrutinib in Previously Treated Subjects with High Risk Chronic Lymphocytic Leukemia

Summary:
Chronic Lymphocytic Leukaemia (CLL) is a cancer of B cells (a type of white blood cell) that predominantly affects the elderly population.
Chemoimmunotherapy has become a standard for the treatment of young and/or fit individuals with CLL who require treatment. However, elderly subjects and those with pre exisiting diseases are often unable to tolerate combination chemoimmunotherapy regimens, or experience inferior outcomes. Ibrutinib, a type of orally administered drug called a Btk inhibitor, was recently approved for certain groups of patients with CLL and has shown favourable outcomes for these patients. ACP-196 has recently been identified and is also an orally administered Btk inhibitor but inhibits more selectively than Ibrubtinib ACP-196 has been well tolerated in healthy volunteers and patients with CLL and has shown sustained improvement in symptoms of CLL.
This study, sponsored by Acerta Pharma, will investigate if ACP-196 is as effective as Inbrutinib and if it is safe. 500 patients over the age of 18 will take part over 100 sites globally with approximately 7 hospitals in the UK. Half the patients will receive Inbrutinib and half will receive ACP-196. Patients will be randomised (by chance) to the study treatment and will know which treatment they are receiving.
Each patient will give informed consent and will be screened for suitability and will be in the study for approximately 4 years unless early withdrawal is necessary. Patients will visit their study doctor every week for 9 weeks and then every 12 weeks and will undergo tests per the schedule in the study protocol such as physical examinations, vital signs, complete diaries and questionaires, blood tests for safety and effectiveness of study drugs, CT scans and ECG.

Inclusion criteria:
Key Inclusion Criteria are:
Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
o Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 Bcell marker (CD19, CD20, or CD23) and CD5.
o Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
o No evidence of cyclin D1 rearrangement or BCL-1
over expression.
• Must have ≥ 1 of the following high-risk prognostic factors:
o Presence of 17p del by central laboratory
o Presence of 11q del by central laboratory
• Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:
o Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin 50% over a 2-month period or a lymphocyte doubling time (LDT) of 1 month before Screening without evidence of infection.
• Measurable nodal disease by computed tomography (CT). Measurable nodal disease is defined as ≥ 1 lymph node > 1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may
be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended.
• Must have received ≥ 1 prior therapies for CLL.
• Meet the following laboratory parameters:
o Absolute neutrophil count (ANC) ≥ 750 cells/μL (0.75 x 109/L) or ≥ 500 cells/μL (0.50 x 109/L) in subjects with
documented bone marrow involvement and independent of growth factor support 7 days before assessment.
o Platelet count ≥ 30,000 cells/μL (30 x 109/L) without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
o Serum aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT) 45 years of age and without menses for > 1 year) and surgically sterilized women are exempt from this criterion.
• Men must agree to use acceptable methods of contraception during the study and for 30 days after the last dose of ACP-196 or ibrutinib if sexually active with a woman of childbearing potential.
• Men must agree to refrain from sperm donation during the study and for 30 days after the last dose of ACP-196
or ibrutinib.
• Are willing and able to adhere to the study visit schedule, understand and comply with other protocol requirements, and provide written informed consent and authorisation to use protected health information. Note vulnerable subjects are not allowed on this protocol (eg, prisoners or institutionalised participants).

Exclusion criteria:
Key Exclusion Criteria are:
Known central nervous system (CNS) lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter’s syndrome.
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) defined as declining hemoglobin or platelet count secondary to
autoimmune destruction within the screening period or
requirement for high doses of steroids (> 20 mg daily of
prednisone daily or equivalent).
• Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor (eg, Bruton tyrosine kinase [Btk] inhibitors or phosphoinositide-3 [PI3] kinase inhibitors or Syk inhibitors) or a BCL-2 inhibitor (eg, ABT199).
• Received any chemotherapy, external beam radiation
therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
• Corticosteroid use > 20 mg within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. Subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded.
• Prior radio-or toxin-conjugated antibody therapy.
• Prior allogeneic stem cell transplant or autologous transplant.
• Major surgery within 4 weeks before first dose of study drug.
• History of prior malignancy except for the following:
Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years before Screening and felt to be at low risk for recurrence by treating physician
o Adequately treated lentigo maligna melanoma without
current evidence of disease or adequately controlled
non-melanomatous skin cancer
o Adequately treated cervical carcinoma in situ without
current evidence of disease
• Currently active clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infarction within 6 months before first dose with study drug.
• Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) or ongoing intravenous anti-infective treatment.
• Known history of infection with human immunodeficiency virus (HIV).
• Serologic status reflecting active hepatitis B or C infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.
• History of stroke or intracranial hemorrhage within 6 months before randomization.
• History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
• Requires or receiving anticoagulation with warfarin or
equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
• Requires treatment with a strong cytochrome P450 3A4
(CYP3A4) inhibitor/inducer.
• Requires treatment with longacting proton pump inhibitors(eg,omeprazole,esomeprazole, lansoprazole,dexlansoprazole, rabeprazole, or pantoprazole)Breast feeding or pregnant.
• Concurrent participation in another therapeutic clinical trial.

Principal Investigator for this trial: Dr Christopher P Fox

Research Ethics Committee Reference: 15/NW/0492

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A prospective singlearm, observational clinical followup study on the application of PHAryngeal electrical stimulation for treatment of neurogenic Dysphagia: a European Registry (PHADER).

Summary:
Patients suffering from a variety of conditions such as Stroke, Parkinson’s Disease or artificial ventilation typically experience difficulty with swallowing known as ‘neurogenic dysphagia’. A common consequence of difficult swallowing is tha… Continue reading

International randomised controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma

Summary:
rEECur is a randomised study to compare four chemotherapy regimens to see which is the best at treating recurrent or refractory Ewing sarcoma. Ewing sarcoma is a type of bone cancer. Recurrent Ewing sarcoma means Ewing sarcoma that has come back after being treated. Refractory Ewing sarcoma means Ewing sarcoma that has grown or progressed while being treated. Ewing sarcoma is rare and running a study such as this requires funding and
collaboration across many different treatment centres and countries. The logistics behind running such a study are
not trivial and as a result rEECur is the first study to directly compare different chemotherapy regimens in this disease setting.
Most doctors treat recurrent and refractory Ewing sarcoma with chemotherapy. However, although several
chemotherapy regimens are available to treat this disease, we do not know which is the best regimen to use. We are
primarily interested in finding out which regimen is most effective at making tumour deposits shrink and, in the longer term, at curing the disease or providing prolonged disease control. We will also determine which regimen has the most side effects, which is associated with the most time spent in hospital and which has the greatest effect on quality of life.
The results will help us to know which chemotherapy regimen is the best to use for patients with this disease. It will also allow us to inform patients about the relative burden of side effects associated with each regimen, allowing individual patients and/or parents to make an informed choice about how to be treated.

Inclusion criteria:
1. Histologically confirmed Ewing sarcoma.
2. Disease recurrence or progression after completion of first line treatment OR Refractory disease, defined by progression during first line treatment or within 12 weeks of its completion. Disease progression will be based on Response Evaluation Criteria In Solid Tumors (RECIST). The appearance of new bone lesions on bone scan will require confirmation with cross-sectional imaging.
3. Soft tissue disease component evaluable by cross-sectional imaging. Patients with bone disease without a
measurable soft tissue component or bone marrow disease only will be eligible for the study but will not contribute to
the phase II primary outcome measure.
4. Age ≥4 years and Exclusion criteria:
1.Bone marrow infiltration resulting in absolute neutrophil count (ANC) Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 14/NW/1110

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

International randomised controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma

Summary:
rEECur is a randomised study to compare four chemotherapy regimens to see which is the best at treating recurrent or refractory Ewing sarcoma. Ewing sarcoma is a type of bone cancer. Recurrent Ewing sarcoma means Ewing sarcoma that has come back after being treated. Refractory Ewing sarcoma means Ewing sarcoma that has grown or progressed while being treated. Ewing sarcoma is rare and running a study such as this requires funding and
collaboration across many different treatment centres and countries. The logistics behind running such a study are
not trivial and as a result rEECur is the first study to directly compare different chemotherapy regimens in this disease setting.
Most doctors treat recurrent and refractory Ewing sarcoma with chemotherapy. However, although several
chemotherapy regimens are available to treat this disease, we do not know which is the best regimen to use. We are
primarily interested in finding out which regimen is most effective at making tumour deposits shrink and, in the longer term, at curing the disease or providing prolonged disease control. We will also determine which regimen has the most side effects, which is associated with the most time spent in hospital and which has the greatest effect on quality of life.
The results will help us to know which chemotherapy regimen is the best to use for patients with this disease. It will also allow us to inform patients about the relative burden of side effects associated with each regimen, allowing individual patients and/or parents to make an informed choice about how to be treated.

Inclusion criteria:
1. Histologically confirmed Ewing sarcoma.
2. Disease recurrence or progression after completion of first line treatment OR Refractory disease, defined by progression during first line treatment or within 12 weeks of its completion. Disease progression will be based on Response Evaluation Criteria In Solid Tumors (RECIST). The appearance of new bone lesions on bone scan will require confirmation with cross-sectional imaging.
3. Soft tissue disease component evaluable by cross-sectional imaging. Patients with bone disease without a
measurable soft tissue component or bone marrow disease only will be eligible for the study but will not contribute to
the phase II primary outcome measure.
4. Age ≥4 years and Exclusion criteria:
1.Bone marrow infiltration resulting in absolute neutrophil count (ANC) Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 14/NW/1110

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Pilot study to investigate the early prediction of toxicity following induction chemotherapy in Ewing’s sarcoma by bloodborne biomarkers and correlation with agedependent pharmacokinetic variation

Summary:
Ewing’s sarcoma is a bone cancer most commonly diagnosed in teenagers. Current treatment strategies result in approximately 60% of patients being cured but with serious sideeffects often associated with treatment. Routine tests do not accurately predict who will be cured or will experience increased side effects. By learning about what happens to the key drugs administered to Ewing’s sarcoma patients following administration, how they are broken down and what factors are important in determining response and toxicity, we will look to improve treatment strategies. This may be particularly important for teenagers and young adults, who may handle drugs differently than younger children. Modifying drug doses for different patient groups will allow the achievement of drug exposures which are most likely to be beneficial, whilst minimising commonly observed and often severe sideeffects. As part of the same clinical trial we shall also perform a series of blood tests that predict sideeffects of chemotherapy in some adult patients, to see if they are helpful in children to allow us to target those children for extra support and treatment. Improved management of cancer patients is anticipated by adjusting treatment of future patients based on differences in drug exposure and expression of biomarkers predictive of response to treatment and toxicity. Although the study focuses on children with Ewing’s sarcoma, the drugs involved in the treatment of this disease and the findings of the study will be applicable across many different types of sarcoma.

Inclusion criteria:
a) Diagnosis of histologically confirmed Ewing sarcoma. b) Receiving VIDE or VDC/IE as part of standard clinical treatment. c) Single or double lumen central venous catheter in place. d) Written informed consent. e) Protocol approval by national and local ethics committee, regulatory authority and Trust R&D Departments.

Exclusion criteria:
a) Receiving nonstandard dose chemotherapy. b) Glomerular filtration rate Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 13/NE/0225

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Pilot study to investigate the early prediction of toxicity following induction chemotherapy in Ewing’s sarcoma by bloodborne biomarkers and correlation with agedependent pharmacokinetic variation

Summary:
Ewing’s sarcoma is a bone cancer most commonly diagnosed in teenagers. Current treatment strategies result in approximately 60% of patients being cured but with serious sideeffects often associated with treatment. Routine tests do not accurately predict who will be cured or will experience increased side effects. By learning about what happens to the key drugs administered to Ewing’s sarcoma patients following administration, how they are broken down and what factors are important in determining response and toxicity, we will look to improve treatment strategies. This may be particularly important for teenagers and young adults, who may handle drugs differently than younger children. Modifying drug doses for different patient groups will allow the achievement of drug exposures which are most likely to be beneficial, whilst minimising commonly observed and often severe sideeffects. As part of the same clinical trial we shall also perform a series of blood tests that predict sideeffects of chemotherapy in some adult patients, to see if they are helpful in children to allow us to target those children for extra support and treatment. Improved management of cancer patients is anticipated by adjusting treatment of future patients based on differences in drug exposure and expression of biomarkers predictive of response to treatment and toxicity. Although the study focuses on children with Ewing’s sarcoma, the drugs involved in the treatment of this disease and the findings of the study will be applicable across many different types of sarcoma.

Inclusion criteria:
a) Diagnosis of histologically confirmed Ewing sarcoma. b) Receiving VIDE or VDC/IE as part of standard clinical treatment. c) Single or double lumen central venous catheter in place. d) Written informed consent. e) Protocol approval by national and local ethics committee, regulatory authority and Trust R&D Departments.

Exclusion criteria:
a) Receiving nonstandard dose chemotherapy. b) Glomerular filtration rate Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 13/NE/0225

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Templates and Forms

Please refer to this page frequently to ensure the correct template or form is used.
All templates and forms are linked to a Standard Operating Procedure (SOP)
TAFQ00701 Standard Operating Procedure Signature Log
Please note some of the forms listed below are also … Continue reading

Hemostasis of Active GI Luminal Tract Bleeding (HALT)(study # 10017)

Summary:
Duodenal and gastric ulcers (termed peptic ulcers) are common occurences. Bleeding from these ulcers is one of the
commonest reasons for admission to hospital causing significant clinical and economic burden and resulting in
17,000-20,000
hospital admissions per year in the UK. In the last two decades there have been major advances in the clinical and
endoscopic management of peptic ulcer bleeding. However, mortality remains high at around 10%,particularly in the
elderly and in those with significant other diseases. The National Institute for Clinical Excellence
(NICE) has issued guidance on the management of peptic ulcer bleeds and recommend the early use of endoscopy
(an instrument used to visualize the gastrointestinal tract) to diagnose the source of bleeding and to provide
treatment.Currently we use three different modalities to treat peptic ulcer bleeding: a) injection of adrenaline, b)the use
of electrocautery and c)the use of mechanical devices such as clips. Most of these techniques require direct tissue
contact to stop the bleeding and this can be technically challenging. Therefore, in a number of cases either the
bleeding cannot be controlled at the time of the index endoscopy or there is recurrent bleeding within 72 hours of the
first bleed. Recently a new technique called Hemospray (Cook Medical) has been shown to be effective in controlling
bleeding from peptic ulcers. This technique utilises application of non toxic proprietary powder that is applied onto the
bleeding site via endoscope using a catheter in short spray bursts. The powder adheres to the bleeding source and
rapidly achieve control of bleeding. This study will evaluate the effectiveness of Hemospray to control the more serious
(NICE) has issued guidance on the management of peptic ulcer bleeds and recommend the early use of endoscopy
(an instrument used to visualize the gastrointestinal tract) to diagnose the source of bleeding and to provide
treatment.Currently we use three different modalities to treat peptic ulcer bleeding: a) injection of adrenaline, b)the use
of electrocautery and c)the use of mechanical devices such as clips. Most of these techniques require direct tissue
contact to stop the bleeding and this can be technically challenging. Therefore, in a number of cases either the
bleeding cannot be controlled at the time of the index endoscopy or there is recurrent bleeding within 72 hours of the
first bleed. Recently a new technique called Hemospray (Cook Medical) has been shown to be effective in controlling
bleeding from peptic ulcers. This technique utilises application of non toxic proprietary powder that is applied onto the
bleeding site via endoscope using a catheter in short spray bursts. The powder adheres to the bleeding source and
rapidly achieve control of bleeding. This study will evaluate the effectiveness of Hemospray to control the more serious
bleeds from peptic ulcers (termed Forrest Ia and Ib)

Inclusion criteria:
Patient requires hemostasis for nonvariceal GI bleeding. Specifically, the patient must have an actively bleeding peptic
ulcer with a Forrest score of 1a or 1b (spurting or oozing)

Exclusion criteria:
 Patient is 1.5

Principal Investigator for this trial: Dr Krish Ragunath

Research Ethics Committee Reference: 13/YH/0334

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Hemostasis of Active GI Luminal Tract Bleeding (HALT)(study # 10017)

Summary:
Duodenal and gastric ulcers (termed peptic ulcers) are common occurences. Bleeding from these ulcers is one of the
commonest reasons for admission to hospital causing significant clinical and economic burden and resulting in
17,000-20,000
hospital admissions per year in the UK. In the last two decades there have been major advances in the clinical and
endoscopic management of peptic ulcer bleeding. However, mortality remains high at around 10%,particularly in the
elderly and in those with significant other diseases. The National Institute for Clinical Excellence
(NICE) has issued guidance on the management of peptic ulcer bleeds and recommend the early use of endoscopy
(an instrument used to visualize the gastrointestinal tract) to diagnose the source of bleeding and to provide
treatment.Currently we use three different modalities to treat peptic ulcer bleeding: a) injection of adrenaline, b)the use
of electrocautery and c)the use of mechanical devices such as clips. Most of these techniques require direct tissue
contact to stop the bleeding and this can be technically challenging. Therefore, in a number of cases either the
bleeding cannot be controlled at the time of the index endoscopy or there is recurrent bleeding within 72 hours of the
first bleed. Recently a new technique called Hemospray (Cook Medical) has been shown to be effective in controlling
bleeding from peptic ulcers. This technique utilises application of non toxic proprietary powder that is applied onto the
bleeding site via endoscope using a catheter in short spray bursts. The powder adheres to the bleeding source and
rapidly achieve control of bleeding. This study will evaluate the effectiveness of Hemospray to control the more serious
(NICE) has issued guidance on the management of peptic ulcer bleeds and recommend the early use of endoscopy
(an instrument used to visualize the gastrointestinal tract) to diagnose the source of bleeding and to provide
treatment.Currently we use three different modalities to treat peptic ulcer bleeding: a) injection of adrenaline, b)the use
of electrocautery and c)the use of mechanical devices such as clips. Most of these techniques require direct tissue
contact to stop the bleeding and this can be technically challenging. Therefore, in a number of cases either the
bleeding cannot be controlled at the time of the index endoscopy or there is recurrent bleeding within 72 hours of the
first bleed. Recently a new technique called Hemospray (Cook Medical) has been shown to be effective in controlling
bleeding from peptic ulcers. This technique utilises application of non toxic proprietary powder that is applied onto the
bleeding site via endoscope using a catheter in short spray bursts. The powder adheres to the bleeding source and
rapidly achieve control of bleeding. This study will evaluate the effectiveness of Hemospray to control the more serious
bleeds from peptic ulcers (termed Forrest Ia and Ib)

Inclusion criteria:
Patient requires hemostasis for nonvariceal GI bleeding. Specifically, the patient must have an actively bleeding peptic
ulcer with a Forrest score of 1a or 1b (spurting or oozing)

Exclusion criteria:
 Patient is 1.5

Principal Investigator for this trial: Dr Krish Ragunath

Research Ethics Committee Reference: 13/YH/0334

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing’s Sarcoma Family of Tumours

Summary:
The treatment for Ewing’s sarcoma consists of three phases: induction chemotherapy, local control (surgery and/or radiotherapy) and consolidation chemotherapy. The Euro Ewing 2012 trial is an international, phase III, openlabel, randomised controlled trial which asks several research questions simultaneously. All patients are randomised at trial entry to receive either the current European treatment strategy or the American equivalent. The European strategy consists of VIDE induction chemotherapy and VAI/VAC (riskadapted) consolidation chemotherapy, whilst the American strategy consists of compressed VDC/IE induction chemotherapy and IE/VC consolidation chemotherapy. The objective is to compare these two strategies with respect to clinical outcome and toxicity. There are three options for randomisation at R2 depending on the patient’s disease status at diagnosis and response following induction chemotherapy. Patients fall into one of the following groups: 1) localised disease and good histological response/small tumour volume these patients are eligible for R2zol 2) localised disease and poor histological response/large tumour volume these patients are eligible for R2loc 3) pulmonary/pleural metastases at diagnosis these patients are eligible for R2pulm The objectives of the R2zol randomisation is to determine whether the addition of zoledronic acid to consolidation chemotherapy is associated with improved clinical outcome. The objective of the R2loc and R2pulm randomisations is to compare highdose chemotherapy (busulfan and melphalan) and stem cell transplantation support with the assigned consolidation chemotherapy from the R1 randomisation.

Inclusion criteria:
· Histologically confirmed ESFT of bone or soft tissue · Localised or pulmonary and/or pleural metastatic disease · Age >2 years and Exclusion criteria:
· Extrapulmonary metastatic disease · Contraindication to the treatment in either of the R1 treatment arms · Second malignancy · Pregnant or breastfeeding women · Followup not possible due to social, geographic or psychological reasons

Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 12/NW/0827

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

International Randomised Controlled Trial for the Treatment of Newly Diagnosed Ewing’s Sarcoma Family of Tumours

Summary:
The treatment for Ewing’s sarcoma consists of three phases: induction chemotherapy, local control (surgery and/or radiotherapy) and consolidation chemotherapy. The Euro Ewing 2012 trial is an international, phase III, openlabel, randomised controlled trial which asks several research questions simultaneously. All patients are randomised at trial entry to receive either the current European treatment strategy or the American equivalent. The European strategy consists of VIDE induction chemotherapy and VAI/VAC (riskadapted) consolidation chemotherapy, whilst the American strategy consists of compressed VDC/IE induction chemotherapy and IE/VC consolidation chemotherapy. The objective is to compare these two strategies with respect to clinical outcome and toxicity. There are three options for randomisation at R2 depending on the patient’s disease status at diagnosis and response following induction chemotherapy. Patients fall into one of the following groups: 1) localised disease and good histological response/small tumour volume these patients are eligible for R2zol 2) localised disease and poor histological response/large tumour volume these patients are eligible for R2loc 3) pulmonary/pleural metastases at diagnosis these patients are eligible for R2pulm The objectives of the R2zol randomisation is to determine whether the addition of zoledronic acid to consolidation chemotherapy is associated with improved clinical outcome. The objective of the R2loc and R2pulm randomisations is to compare highdose chemotherapy (busulfan and melphalan) and stem cell transplantation support with the assigned consolidation chemotherapy from the R1 randomisation.

Inclusion criteria:
· Histologically confirmed ESFT of bone or soft tissue · Localised or pulmonary and/or pleural metastatic disease · Age >2 years and Exclusion criteria:
· Extrapulmonary metastatic disease · Contraindication to the treatment in either of the R1 treatment arms · Second malignancy · Pregnant or breastfeeding women · Followup not possible due to social, geographic or psychological reasons

Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 12/NW/0827

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A pilot study to assess the efficacy of intravenous iron isomaltoside 1000 (Monofer) in the management of anaemia associated with the palliative management of upper gastrointestinal adenocarcinoma.

Summary:
There are approximately 16,000 people diagnosed with cancer of the stomach or gullet each year. Unfortunately, these cancers are often inoperable at the time of diagnosis, leaving palliative chemotherapy as the only treatment option available. This chemotherapy regimen is potentially a lengthy course of treatment lasting up to 6 months. As the primary tumour is not removed, it may continue to bleed over this period causing the patient to chronically lose blood, and anaemia to develop. This can be worsened by the side effects of chemotherapy and compounded by reduced oral intake due to swallowing problems from the tumours themselves. Anaemia is associated with symptoms such as breathlessness, chest pain, lethargy and dizziness. If untreated, these symptoms can seriously impact on patients’ quality of life and the ability to complete chemotherapy. Oral iron supplementation has been the mainstay of outpatient treatment for such anaemia. However, some patients do not tolerate it due to gastrointestinal sideeffects and difficulty swallowing the tablets due to the tumour. If such measures fail, then blood transfusions may be required. These are associated with the risk of transmission of infection and allergic reactions, hence clinicians often have a higher threshold for administrating them to treat patients’ symptoms. Intravenous iron has been used effectively to treat anaemia in other conditions but there is a lack of evidence to prove it’s use in this context. This study thus aims to investigate the efficacy and safety of intravenous iron in the palliative management of upper gastrointestinal cancers.

Inclusion criteria:
1.Anaemic as defined by local laboratory normal range(MalesExclusion criteria:
1. Patients who following investigation do not have a histological diagnosis of upper GI adenocarcinoma. 2. Female participants who are pregnant, lactating or planning a pregnancy during the course of the study. 3. Patients with evidence of iron overload or disturbances in utilisation of iron as stated in the product SPC. 4. Known haematological disease that, in the investigators opinion would confound any changes in blood results. 5. Features necessitating urgent surgery at inclusion 6. Previous allergy to intravenous iron or related iron products. 7. Patients who are unable to consent. 8. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study. 9. Donation of blood during the study. 10.Prisoners and minors (Principal Investigator for this trial: Mr Oliver Ng

Research Ethics Committee Reference: 13/EM/0069

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

A pilot study to assess the efficacy of intravenous iron isomaltoside 1000 (Monofer) in the management of anaemia associated with the palliative management of upper gastrointestinal adenocarcinoma.

Summary:
There are approximately 16,000 people diagnosed with cancer of the stomach or gullet each year. Unfortunately, these cancers are often inoperable at the time of diagnosis, leaving palliative chemotherapy as the only treatment option available. This chemotherapy regimen is potentially a lengthy course of treatment lasting up to 6 months. As the primary tumour is not removed, it may continue to bleed over this period causing the patient to chronically lose blood, and anaemia to develop. This can be worsened by the side effects of chemotherapy and compounded by reduced oral intake due to swallowing problems from the tumours themselves. Anaemia is associated with symptoms such as breathlessness, chest pain, lethargy and dizziness. If untreated, these symptoms can seriously impact on patients’ quality of life and the ability to complete chemotherapy. Oral iron supplementation has been the mainstay of outpatient treatment for such anaemia. However, some patients do not tolerate it due to gastrointestinal sideeffects and difficulty swallowing the tablets due to the tumour. If such measures fail, then blood transfusions may be required. These are associated with the risk of transmission of infection and allergic reactions, hence clinicians often have a higher threshold for administrating them to treat patients’ symptoms. Intravenous iron has been used effectively to treat anaemia in other conditions but there is a lack of evidence to prove it’s use in this context. This study thus aims to investigate the efficacy and safety of intravenous iron in the palliative management of upper gastrointestinal cancers.

Inclusion criteria:
1.Anaemic as defined by local laboratory normal range(MalesExclusion criteria:
1. Patients who following investigation do not have a histological diagnosis of upper GI adenocarcinoma. 2. Female participants who are pregnant, lactating or planning a pregnancy during the course of the study. 3. Patients with evidence of iron overload or disturbances in utilisation of iron as stated in the product SPC. 4. Known haematological disease that, in the investigators opinion would confound any changes in blood results. 5. Features necessitating urgent surgery at inclusion 6. Previous allergy to intravenous iron or related iron products. 7. Patients who are unable to consent. 8. Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study. 9. Donation of blood during the study. 10.Prisoners and minors (Principal Investigator for this trial: Mr Austin Acheson

Research Ethics Committee Reference: 13/EM/0069

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

SIOP CNS GCT II. Prospective Trial for the diagnosis and treatment of children, adolescents and young adults with Intracranial Germ Cell Tumours

Summary:
Intracranial germ cell tumours (GCTs) are rare tumours of childhood and adolescence that are varied with respect to their primary site, histology, biological profile and response to treatment. This trial is attempting to distinguish these different tumours by virtue of these factors, and treat accordingly. The philosophy is that the worse the prognosis (in relative terms), the more aggressive the treatment needs to be. In malignant GCTs, initial combination platinumbased chemotherapy will be administered prior to risk adapted radiotherapy and delayed tumour resection where required. In tumours with mixed histology, the therapeutic approach depends on the component with the highest grade of malignancy. For teratoma, no standardized treatment approach has been investigated in a multinational protocol to date.

Inclusion criteria:
Note: Given the rarity of the disease and the aims of the trial, inclusion criteria are necessarily broad: Primary diagnosis of an intracranial germ cell tumour Main residence in one of the participating countries Written consent for trial participation, diagnosis and treatment according to the protocol and consent for data transfer

Exclusion criteria:
Primary diagnosis predating the opening of SIOP CNS GCT II Patients with CNS GCTs as second malignancies Patients in whom treatment according to CNS GCT II is not intended Patients with a medical, psychiatric or social condition incompatible with protocol treatment Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc. Pregnancy and lactation Any treatment not given according to protocol prior to registration

Principal Investigator for this trial: Professor Richard Grundy

Research Ethics Committee Reference: 12/EE/0271

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

SIOP CNS GCT II. Prospective Trial for the diagnosis and treatment of children, adolescents and young adults with Intracranial Germ Cell Tumours

Summary:
Intracranial germ cell tumours (GCTs) are rare tumours of childhood and adolescence that are varied with respect to their primary site, histology, biological profile and response to treatment. This trial is attempting to distinguish these different tumours by virtue of these factors, and treat accordingly. The philosophy is that the worse the prognosis (in relative terms), the more aggressive the treatment needs to be. In malignant GCTs, initial combination platinumbased chemotherapy will be administered prior to risk adapted radiotherapy and delayed tumour resection where required. In tumours with mixed histology, the therapeutic approach depends on the component with the highest grade of malignancy. For teratoma, no standardized treatment approach has been investigated in a multinational protocol to date.

Inclusion criteria:
Note: Given the rarity of the disease and the aims of the trial, inclusion criteria are necessarily broad: Primary diagnosis of an intracranial germ cell tumour Main residence in one of the participating countries Written consent for trial participation, diagnosis and treatment according to the protocol and consent for data transfer

Exclusion criteria:
Primary diagnosis predating the opening of SIOP CNS GCT II Patients with CNS GCTs as second malignancies Patients in whom treatment according to CNS GCT II is not intended Patients with a medical, psychiatric or social condition incompatible with protocol treatment Participation within a different trial for treatment of germ cell tumours and/or concurrent treatment within any other clinical trial. The only exceptions to this are trials with different endpoints, involving aspects of supportive treatment which can run parallel to SIOP CNS GCT II without influencing the outcome of this trial e.g. trials on antiemetics, antimycotics, antibiotics, strategies for psychosocial support etc. Pregnancy and lactation Any treatment not given according to protocol prior to registration

Principal Investigator for this trial: Professor Richard Grundy

Research Ethics Committee Reference: 12/EE/0271

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

ION? Is ablative radiOiodine Necessary for low risk differentiated thyroid cancer patients

Summary:
Total thryroidectomy(surgery to remove the thyroid gland) followed by Radioactive Iodine Ablation is the standard treatment for patients presenting with intermediate or high risk well differentiated thyroid cancer. Radioiodine (RAI) is mainly used to eliminate any residual normal thyroid tissue. In a subgroup of patients characterised as having low risk of recurrence there is debate as to whether ablation represents overtreatment. RAI causes many side effects including increased risk of a second primary cancer. IoN will answer the question of whether RAI is necessary for low risk differentiated thyroid cancer patients who already have been offered the other two important modalities of treatment i.e. Total Thyroidectomy and optimal TSH (Thyroid Stimulating Hormone) suppression. Patients who have undergone a total thyroidectomy will be randomised (allocated randomly) into one of two groups by a computer program. One group will receive ablation at an activity of 1.1 GBq (Giga Becquerels), the other will not receive ablation. There will be an equal number of patients in both groups. The study is being funded by Cancer Research UK and has a phase II component to assess whether recruitment is feasible before moving to a phase III study. 570 patients will be recruited for the study.

Inclusion criteria:
1. R0 total thyroidectomy (in one or two stages, no residual disease present) within the last 6 months 2. Negative pregnancy test in women of child bearing potential 3. Aged 16 or over 4. WHO performance status 0 ­ 2, self caring 5. Histological confirmation of differentiated thyroid carcinoma: Papillary thyroid cancer a. Non aggressive histological features (small foci of aggressive histology allowed) b. pT1b (12cm), intrathyroidal c. pT2 (24cm), intrathyroidal d. pT3, intrathyroidal only e. Multifocal microcarcinoma f. pN0 g. pN1a h. pNX Follicular thyroid cancer/ Hürthle cell cancer (minimally invasive with capsular invasion only) a. pT1b (1 2cm), pT2 (24cm) intrathyroidal

Exclusion criteria:
1. Papillary and Follicular carcinoma which is unifocal and Principal Investigator for this trial: Dr Eleanor James

Research Ethics Committee Reference: 11/NE/0228

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

ION? Is ablative radiOiodine Necessary for low risk differentiated thyroid cancer patients

Summary:
Total thryroidectomy(surgery to remove the thyroid gland) followed by Radioactive Iodine Ablation is the standard treatment for patients presenting with intermediate or high risk well differentiated thyroid cancer. Radioiodine (RAI) is mainly used to eliminate any residual normal thyroid tissue. In a subgroup of patients characterised as having low risk of recurrence there is debate as to whether ablation represents overtreatment. RAI causes many side effects including increased risk of a second primary cancer. IoN will answer the question of whether RAI is necessary for low risk differentiated thyroid cancer patients who already have been offered the other two important modalities of treatment i.e. Total Thyroidectomy and optimal TSH (Thyroid Stimulating Hormone) suppression. Patients who have undergone a total thyroidectomy will be randomised (allocated randomly) into one of two groups by a computer program. One group will receive ablation at an activity of 1.1 GBq (Giga Becquerels), the other will not receive ablation. There will be an equal number of patients in both groups. The study is being funded by Cancer Research UK and has a phase II component to assess whether recruitment is feasible before moving to a phase III study. 570 patients will be recruited for the study.

Inclusion criteria:
1. R0 total thyroidectomy (in one or two stages, no residual disease present) within the last 6 months 2. Negative pregnancy test in women of child bearing potential 3. Aged 16 or over 4. WHO performance status 0 ­ 2, self caring 5. Histological confirmation of differentiated thyroid carcinoma: Papillary thyroid cancer a. Non aggressive histological features (small foci of aggressive histology allowed) b. pT1b (12cm), intrathyroidal c. pT2 (24cm), intrathyroidal d. pT3, intrathyroidal only e. Multifocal microcarcinoma f. pN0 g. pN1a h. pNX Follicular thyroid cancer/ Hürthle cell cancer (minimally invasive with capsular invasion only) a. pT1b (1 2cm), pT2 (24cm) intrathyroidal

Exclusion criteria:
1. Papillary and Follicular carcinoma which is unifocal and Principal Investigator for this trial: Dr Sally Ann Morgan

Research Ethics Committee Reference: 11/NE/0228

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

First international InterGroup Study for nodular Lymphocytepredominant Hodgkin’s Lymphoma in Children and Adolescents

Summary:
This European study of nodular Lymphocyte Predominant Hodgkin’s Lymphoma will ascertain whether children with early stage disease [stages IA & IIA] can be managed safely with surgery and little or no chemotherapy. If the disease is completely resected a “Watch and Wait” approach is adopted otherwise patients will receive three cycles of non intensive chemotherapy.

Inclusion criteria:
Inclusion criteria: · Nodular lymphocytepredominant Hodgkin’s lymphoma confirmed by reference pathology. · Initial stage IA/IIA (according to local staging) or relapse stage IA or IIA and residual tumour after relapse biopsy and no additional surgery planned in nLP patients relapsing after surgery alone · Patient aged under 18 years at time of diagnosis · Written informed consent of the patient and/or the patient’s parents or guardian according to national laws In certain European countries very young patients may have to be excluded in order to comply with national laws or formal insurance requirements.

Exclusion criteria:
Exclusion criteria: · Pretreatment of Hodgkin’s lymphoma differing from study protocol · Any extranodal involvement · Inability to fulfil protocol requirements for imaging (CT, MRI, FDGPET) at staging and response assessment · Known hypersensitivity or contraindication to study drugs · Prior chemotherapy or radiotherapy · Current or recent therapy (within 30 days prior to the start of trial treatment) with steroids · Current or recent (within 30 days prior to the start of trial treatment) treatment with another investigational drug or participation in another investigational trial · Other (simultaneous) malignancies · Severe concomitant diseases (e.g. immune deficiency syndrome) · Known HIV positivity · Pregnancy and / or lactation · Females who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile) (except for surgery only. Subsequent exclusion criteria: Patients are excluded from the study after registration if: · Documents or material ascertained before study inclusion show that an exclusion criterion was fulfilled or an inclusion criterion was not met · The patient and/or the patient’s parents or guardian withdraw(s) his/her/their consent to further study participation. If central review results in upstaging above stage IA/IIA the patient is still documented in the scope of the study but not eligible for treatment in the study. The patient’s physician then decides together with the patient/parents or guardian as to the most appropriate therapy. The study chairpersons decide on the exclusion along with the biometrician of the study. Subsequent exclusion of a patient can be requested by a trial site only in writing. Subsequent exclusion of a patient differs from an individual therapy withdrawal. In the latter case the treatment of the patient according to protocol is terminated, but followup and documentation (data collection in the CRF) is continued according to protocol and the patient appears in all relevant analyses.

Principal Investigator for this trial: Dr Sophie Wilne

Research Ethics Committee Reference: 11/EM/0358

Contact us about participating in this study by emailing R&IActiveStudyEnquiries@nuh.nhs.uk or telephoning 0115 924 9924 Ext. 70076 Continue reading

Standard Operating Procedures

Please refer to this page frequently to ensure the correct SOP is used
To access templates and forms associated with individual SOPs please refer to Templates and Forms.
All links in this section are direct downloads for pdfs
R&I have reviewed … Continue reading

CLAHRC Briefing on Innovation, Health & Wealth

This CLAHRC NDL briefing concerns recent policy developments in Innovation Health & Wealth. Learn about important changes and plans in this easy to consume summary, together with links to the full details if you need to delve more deeply. This briefing outlines the eight priority areas for improvement and succinct descriptions of the High Impact Innovations which should be introduced with
immediate effect.
Continue reading

Jennie Walker

Jennie Walker
Academic Division of Orthopaedic and Accident Surgery
C floor West Block, Queen’s Medical Centre
0115 924 9924 ext 64170
Jennie.walker@nottingham.ac.uk or Jennie.walker@nuh.nhs.uk
Role
Clinical Educator (part time)
Teaching and assessment of medical undergraduates.
Teaching and professional development of nursing staff within MSKN.
Biography
Graduated from the University … Continue reading

How do I recruit patients and the public and keep them involved?

The Department of Research & Innovation has established a standard operational procedure ‘Recruiting patients and the public’. You may contact Jane Flewitt for additional advice.

This site uses cookies. Find out more about this site’s cookies.