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We are recruiting: Nottingham University Hospitals Research and Innovation Quality Assurance/GCP Auditor

Do you wish to make a difference to research in the NHS? An opportunity has arisen for a Quality Assurance/GCP Auditor to join the Research and Innovation Department at Nottingham University Hospitals (NUH) NHS Trust.
NUH has identified excellence in research … Continue reading

Vacancy: NUH R&I Quality Assurance / GCP Manager, extended to 16th September

NUH R&I seeks to appoint a QA/GCP Manager to assure the quality of clinical research undertaken within Nottingham University Hospitals NHS Trust in accordance with legislative and best practice requirements. This is a key role in the co-ordination of working practices, policy implementation and preparation for external audits and MHRA inspection. Continue reading

Randomized, DoubleBlind, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer

Summary:
Colorectal cancer is the third most common cancer in men and the second most common in women with 746,000 and
614,000 cases respectively worldwide in 2012. Metastatic (cancer that has spread) colorectal cancer (mCRC) is a
largely incurable disease. The majority of patients diagnosed with mCRC have secondary tumors in their liver or lungs. Current approved chemotherapy drug treatment options include FOLFIRI and FOLFOX . These combination chemotherapy treatments may be used with bevacizumab (Avastin), which inhibits the growth of new blood vessels
around tumors. These treatments significantly improve quality and duration of life, but only 6% of patients live to 5 years after diagnosis of mCRC.
Veliparib is a “PARP inhibitor” that may improve chemotherapy. It works by blocking tumour cells from repairing DNAdamage caused by chemotherapy, ultimately killing cancer cells.
In this study patients will receive FOLFIRI (±bevacizumab) and veliparib or placebo (substance that looks the same as
veliparib but has no active ingredients). Half of the patients will receive veliparib, and half placebo. The trial will look at
which treatment is better at controlling the cancer by measuring overall survival and progressionfree
time. This is a phase II, randomised, blinded trial – neither the patient nor the doctor knows whether the patient is taking veliparib or placebo.
Patients could benefit if tumour growth is inhibited, improving their condition and survival time. Information gathered may help improve future treatment of this disease.
Patients will attend regular study visits at hospital until the treatment is no longer effective (10-15 months on average).
The effect of the treatments on the cancer will be monitored by scans, blood tests and checking for side effects. There are additional blood tests to see why some people respond better than others and how long the drug remains in the body and an optional genetics test.

Inclusion criteria:
1. 18 years of age;
2. Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum;
3. At least 1 unresectable lesion on a CT scan that is measurable as defined by RECIST, Version 1.1;
4. ECOG performance score of 0 or 1;
Rationale criteria 1-4 these inclusion criteria were selected to ensure that an appropriate subject population with
sufficient disease severity is selected.
5. Adequate haematologic, renal and hepatic function as follows:
*Bone marrow: Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets ≥ 100,000/mm3; (independent of platelet
transfusions within 3 months prior to starting protocol therapy); Hemoglobin ≥ 9.0 g/dL;
*Renal function: Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min;
*Hepatic function and enzymes: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of institution’s normal range. Subjects with liver metastases may have an AST and ALT of ≤ 5.0 × ULN;
*Bilirubin: ≤ 1.5 × the ULN of institution’s normal range.
Rationale criteria 5 was selected for the safety of subjects.
6. If female, subject must be postmenopausal for at least one year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control until 90 days after the last dose of protocol therapy:
*Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not
acceptable;
*Vasectomized partner(s);
*Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior C1D–2 (if the subject is
currently using a hormonal contraceptive, she should also use a barrier method during the study and for 1 month after
protocol therapy completion);
*Intrauterine device (IUD);
*Doublebarrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or
creams).
7. If male, subject must be surgically sterile or practicing at least one of the following methods of contraception, from the initial protocol therapy administration until 90 days after the last dose of protocol therapy:
*Partner(s) using IUD;
*Partner(s) using hormonal contraceptives (oral, vaginal, parenteral or transdermal);
*Subject and/or partner(s) using doublebarrier
method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or creams);
*Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not
acceptable.
Rationale criteria 6-7 relating to pregnancy were selected as the impact of veliparib on the unborn foetus is not
known. Therefore these criteria are required to ensure that the patients enrolled take adequate precautions to avoid
pregnancy.
8. Subject must be capable of understanding and complying with parameters as outlined in the protocol and able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or studyspecific procedures.
Rationale criteria
8 is in accordance with GCP.
For Subjects Receiving Bevacizumab:
9. Blood pressure must be well controlled (Exclusion criteria:
1. Prior anticancer treatment for metastatic colorectal cancer;
2. Prior exposure to PARP inhibitors;
3. The last course of adjuvant chemotherapy must have ended > 12 months prior to colorectal cancer recurrence;
4. Known Gilbert’s Syndrome;
Rationale criteria 1-4 these inclusion criteria were selected to ensure that an appropriate subject population with
sufficient disease severity is selected.
5. Prior radiotherapy to greater than 25% of bone marrow;
6. Prior radiotherapy ≤ 4 weeks of C1D¨C2;
7. Any type of major surgery ≤ 4 weeks of C1D¨C2;
Rationale criteria 5-7 were selected for the safety of subjects.
8. Previous or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for three years;
9. Known hypersensitivity to irinotecan, 5FU
or folinic acid;
10. Clinically significant and uncontrolled major medical condition(s) including but not limited to:
*Uncontrolled nausea/vomiting/diarrhoea;
*Active uncontrolled infection;
*Unstable angina pectoris or cardiac arrhythmia;
*Psychiatric illness/social situation that would limit compliance with study requirements.
Rationale criteria 9-10 were selected for the safety of subjects.
11. Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline
pattern of > 3 watery of soft stools daily. Subjects with an ileostomy or colostomy may enter the study at the discretion of the Investigator;
12. Subject is pregnant or lactating;
Rationale criteria 12 was selected for the safety of subjects.
13. Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation
within 28 days prior to C1D-2;
14. Any medical condition, which in the opinion of the study Investigator, places the subject at an unacceptably high risk for toxicities.
15. Subject has received an investigational drug within the 28 days prior to Screening;
Rationale criteria 14-15 were selected for the safety of subjects.
16. Any subjects will be excluded if prohibited from participation according to local laws or regulations.
Rationale criteria
16 was selected to ensure that an appropriate subject population with sufficient disease severity is
selected.
For Subjects Receiving Bevacizumab:
17. Prior treatment with bevacizumab;
18. Known central nervous system metastases;
19. Significant history of bleeding events or GI perforation;
*Subjects with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6
months of C1D¨C2 are not eligible unless the source of bleeding has been resected;
*Subjects with a history of GI perforation within 12 months of C1D2
are not eligible;
20. Serious or non-healing wound, ulcer or bone fracture;
21. History of venous or arterial thromboembolism within 2 months of enrollment;
22. Known hypersensitivity to recombinant or murine antibodies.
Rational criteria 17-22 were for the safety of subjects that receive bevacizumab.

Principal Investigator for this trial: Dr Vanessa Potter

Research Ethics Committee Reference: 14/EM/1314

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

Randomized, DoubleBlind, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer

Summary:
Colorectal cancer is the third most common cancer in men and the second most common in women with 746,000 and
614,000 cases respectively worldwide in 2012. Metastatic (cancer that has spread) colorectal cancer (mCRC) is a
largely incurable disease. The majority of patients diagnosed with mCRC have secondary tumors in their liver or lungs. Current approved chemotherapy drug treatment options include FOLFIRI and FOLFOX . These combination chemotherapy treatments may be used with bevacizumab (Avastin), which inhibits the growth of new blood vessels
around tumors. These treatments significantly improve quality and duration of life, but only 6% of patients live to 5 years after diagnosis of mCRC.
Veliparib is a “PARP inhibitor” that may improve chemotherapy. It works by blocking tumour cells from repairing DNAdamage caused by chemotherapy, ultimately killing cancer cells.
In this study patients will receive FOLFIRI (±bevacizumab) and veliparib or placebo (substance that looks the same as
veliparib but has no active ingredients). Half of the patients will receive veliparib, and half placebo. The trial will look at
which treatment is better at controlling the cancer by measuring overall survival and progressionfree
time. This is a phase II, randomised, blinded trial – neither the patient nor the doctor knows whether the patient is taking veliparib or placebo.
Patients could benefit if tumour growth is inhibited, improving their condition and survival time. Information gathered may help improve future treatment of this disease.
Patients will attend regular study visits at hospital until the treatment is no longer effective (10-15 months on average).
The effect of the treatments on the cancer will be monitored by scans, blood tests and checking for side effects. There are additional blood tests to see why some people respond better than others and how long the drug remains in the body and an optional genetics test.

Inclusion criteria:
1. 18 years of age;
2. Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum;
3. At least 1 unresectable lesion on a CT scan that is measurable as defined by RECIST, Version 1.1;
4. ECOG performance score of 0 or 1;
Rationale criteria 1-4 these inclusion criteria were selected to ensure that an appropriate subject population with
sufficient disease severity is selected.
5. Adequate haematologic, renal and hepatic function as follows:
*Bone marrow: Absolute Neutrophil count (ANC) ≥ 1,500/μL; Platelets ≥ 100,000/mm3; (independent of platelet
transfusions within 3 months prior to starting protocol therapy); Hemoglobin ≥ 9.0 g/dL;
*Renal function: Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥ 50 mL/min;
*Hepatic function and enzymes: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × the upper limit of normal (ULN) of institution’s normal range. Subjects with liver metastases may have an AST and ALT of ≤ 5.0 × ULN;
*Bilirubin: ≤ 1.5 × the ULN of institution’s normal range.
Rationale criteria 5 was selected for the safety of subjects.
6. If female, subject must be postmenopausal for at least one year, surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or practicing at least one of the following methods of birth control until 90 days after the last dose of protocol therapy:
*Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not
acceptable;
*Vasectomized partner(s);
*Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior C1D–2 (if the subject is
currently using a hormonal contraceptive, she should also use a barrier method during the study and for 1 month after
protocol therapy completion);
*Intrauterine device (IUD);
*Doublebarrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or
creams).
7. If male, subject must be surgically sterile or practicing at least one of the following methods of contraception, from the initial protocol therapy administration until 90 days after the last dose of protocol therapy:
*Partner(s) using IUD;
*Partner(s) using hormonal contraceptives (oral, vaginal, parenteral or transdermal);
*Subject and/or partner(s) using doublebarrier
method (condoms, contraceptive sponge, diaphragm, or vaginal ring with spermicidal jellies or creams);
*Total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not
acceptable.
Rationale criteria 6-7 relating to pregnancy were selected as the impact of veliparib on the unborn foetus is not
known. Therefore these criteria are required to ensure that the patients enrolled take adequate precautions to avoid
pregnancy.
8. Subject must be capable of understanding and complying with parameters as outlined in the protocol and able to voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or studyspecific procedures.
Rationale criteria
8 is in accordance with GCP.
For Subjects Receiving Bevacizumab:
9. Blood pressure must be well controlled (Exclusion criteria:
1. Prior anticancer treatment for metastatic colorectal cancer;
2. Prior exposure to PARP inhibitors;
3. The last course of adjuvant chemotherapy must have ended > 12 months prior to colorectal cancer recurrence;
4. Known Gilbert’s Syndrome;
Rationale criteria 1-4 these inclusion criteria were selected to ensure that an appropriate subject population with
sufficient disease severity is selected.
5. Prior radiotherapy to greater than 25% of bone marrow;
6. Prior radiotherapy ≤ 4 weeks of C1D¨C2;
7. Any type of major surgery ≤ 4 weeks of C1D¨C2;
Rationale criteria 5-7 were selected for the safety of subjects.
8. Previous or concurrent malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the subject has been disease-free for three years;
9. Known hypersensitivity to irinotecan, 5FU
or folinic acid;
10. Clinically significant and uncontrolled major medical condition(s) including but not limited to:
*Uncontrolled nausea/vomiting/diarrhoea;
*Active uncontrolled infection;
*Unstable angina pectoris or cardiac arrhythmia;
*Psychiatric illness/social situation that would limit compliance with study requirements.
Rationale criteria 9-10 were selected for the safety of subjects.
11. Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline
pattern of > 3 watery of soft stools daily. Subjects with an ileostomy or colostomy may enter the study at the discretion of the Investigator;
12. Subject is pregnant or lactating;
Rationale criteria 12 was selected for the safety of subjects.
13. Subject who requires parenteral nutrition, tube feeding or has evidence of partial bowel obstruction or perforation
within 28 days prior to C1D-2;
14. Any medical condition, which in the opinion of the study Investigator, places the subject at an unacceptably high risk for toxicities.
15. Subject has received an investigational drug within the 28 days prior to Screening;
Rationale criteria 14-15 were selected for the safety of subjects.
16. Any subjects will be excluded if prohibited from participation according to local laws or regulations.
Rationale criteria
16 was selected to ensure that an appropriate subject population with sufficient disease severity is
selected.
For Subjects Receiving Bevacizumab:
17. Prior treatment with bevacizumab;
18. Known central nervous system metastases;
19. Significant history of bleeding events or GI perforation;
*Subjects with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6
months of C1D¨C2 are not eligible unless the source of bleeding has been resected;
*Subjects with a history of GI perforation within 12 months of C1D2
are not eligible;
20. Serious or non-healing wound, ulcer or bone fracture;
21. History of venous or arterial thromboembolism within 2 months of enrollment;
22. Known hypersensitivity to recombinant or murine antibodies.
Rational criteria 17-22 were for the safety of subjects that receive bevacizumab.

Principal Investigator for this trial: Dr Vanessa Potter

Research Ethics Committee Reference: 14/EM/1314

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 2, Randomized, Double-Blind Study of Ipilimumab Administered at 3 mg/kg vs 10 mg/kg in Adult Subjects with Metastatic Chemotherapy-Naïve Castration Resistant Prostate Cancer Who are Asymptomatic or Minimally Symptomatic

Summary:
Prostate cancer is one of the most common cancers in men in the UK. In many patients with metastatic prostate
cancer, the cancer can be slow growing in type, and patients experience no or minimal symptoms. Treatment is not always started at this stage. Treating doctors may decide to watch and wait and keep a close eye on the patient to see if the cancer and symptoms begin to develop. It is typical that most patients will subsequently receive chemotherapy, in line with standard care, when it is clinically appropriate to do so.
The purpose of this study is to compare how well two different doses of ipilimumab works in patients with prostate cancer who are no longer responding to hormone therapy (castration resistant). The study will look at how safe ipilimumab is, and how well it works.
Approximately 200 patients in total are expected to participate in this study, with about 24 patients taking part in the UK. Patients will be assigned 1:1 to either a 3 mg/kg or 10 mg/kg ipilimumab treatment. Ipilimumab is given via a 6100 minute infusion every 3 weeks for a total of 4 infusions, then every 12 weeks for a maximum of 3 years or until treatment stopping criteria are met, unacceptable side effects are experienced or the patient wishes to withdraw. Patients who withdraw from treatment will be followed up. During the study, if there is a spread or growth of cancer, this will be assessed by regular CT and bone scans. Patients will undergo physical examinations and have blood samples taken at all study visits. Patients will also have urine taken; their weight and vital signs measured at some visits, and be asked to fill in questionnaires about pain, wellbeing and health.
The research is funded by BristolMyers
Squibb, and is being conducted globally.

Inclusion criteria:
1. Signed Written Informed Consent to ensure patient rights, safety and wellbeing are protected, and to comply with the Declaration of Helsinki and ICH GCP.
2. Men, at least 18 years of age. Only adults are included because children and women do not suffer from prostate
cancer.
3. Histologically diagnosed prostate cancer with evidence of disease from CT scan, MRI scan or bone scan. This
confirms that patients have the correct diagnosis for the patient population being evaluated in the study.
4. Patients who have progressed while receiving hormonal treatment confirmed by the presence of at least an increase in prostate specific antigen, the appearance of 2 or more new bone lesions or progression in soft tissue.
5. Patients who have had their testicles removed (orchiectomy) or are having hormone therapy to control testosterone (LHRH) and have a testosterone level of less than 50ng/dl.
6. Patients who have discontinued treatment with antiandrogens at least 2 weeks prior to randomisation (drugs that stop/inhibit the effect of male hormones). Use of abiraterone and/or enzalutamide prior to starting study therapy is allowed.
7. ECOG performance status of PS 01 (normal activity with effort or better) since patients who are not as well, would be unlikely to be able to come to clinic for the required visits. Eastern Cooperative Oncology Group (ECOG) performance status is a way of measuring a patients disease progression and how the disease affects the daily living abilities of the patient.
8. Patients who are experiencing minimal symptoms or no symptoms defined as; pain not requiring any pain killers
over a 5 day assessment time period before randomisation to study treatment and; if pain is present, the patient must
rate the pain over a 5 day assessment time period before randomisation to study treatment. It must be confirmed that the patient is not suitable to receive chemotherapy at this stage.
9.the reenrolment of a subject into the study is allowed, that is, had previously been discontinued from the study as a pretreatment failure (i.e. subject had not been randomised or treated).

Exclusion criteria:
1. Men who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 165 days (24 weeks) after the last dose of study medication. It is not known whether the drug may cause harm to a baby.
2. Patients with evidence of brain metastasis.
3. Medical History and Diseases/Conditions which the patient has in addition to the disease under study:
Autoimmune disease (e.g. inflammatory bowel disease including Crohn’s and ulcerative colitis) Symptomatic
disease (e.g. rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, scleroderma, Lupus,
autoimmune vasculitis, autoimmune motor neuropathy (nervous system problems caused by the immune system)
Known HIV, Hepatitis B or Hepatitis C infection (diseases affecting the immune system) Patients who have had radiation to the pelvic area who experienced side effects within the last year Mental health problems or illness or other conditions which mean that the patient is not able to comply with the requirements of the study Less
than 3 years disease free from other malignancies (other cancers)
4. Physical & Laboratory findings:
Inadequate hematologic function (blood cell counts), hepatic function (liver function), renal function (kidney function) and creatinine clearance (metabolism by products) as determined by serum levels within specified ranges. The patient must be healthy enough to undergo and continue treatment without the likelihood of experiencing unnecessary adverse events.
5. Prohibited Treatments & Therapies Prior
treatment with any immunotherapy for prostate cancer
Prior to ongoing chemotherapy for treatment of prostate cancer Radiotherapy to the pelvis area within 3 months prior to the study of study medication Chronic use of immunosuppressant’s or systemic corticosteroids (patients must have an active/working immune system) Nononcology vaccine therapy for prevention of infectious diseases (other treatment that may interfere or interact with
the study drug) Prior treatment with T cell inhibitor or agonist (patients must have a normal working immune system) or radioisotope therapy (e.g. radium, strontium or samaruim) which are radioactive chemicals.
6. Current participation in another research study since the patient would not be able to comply with this study and all
the requirements, and would also affect the information gained from the study.
7. Prisoners or patients who are compulsorily detained (involuntarily imprisoned) for treatment of either a psychiatric or physical illness (e.g., infectious disease) must not be enrolled into this study. This is to avoid the risk of coercion as these patients may not be free to make their own decisions.

Principal Investigator for this trial: Dr Santhanam Sundar

Research Ethics Committee Reference: 14/WS/1133

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

The early use of Antibiotics for at Risk CHildren with InfluEnza in primary care (ARCHIE): a doubleblind randomised placebo controlled trial

Summary:
Flu (influenza) and flulike illness are among the commonest reasons why parents and carers take children to see a doctor or nurse in winter. Flu is a viral infection, which just causes a mild cough or coldlike sypmtoms in most children. However, when some children get flu, they develop bacterial infections, such as chest or ear infections, which can make them feel even more unwell. `At risk’ children with underlying medical conditions (asthma, diabetes, cancer, cerebral palsy, Down’s syndrome, heart problems, kidney problems , liver problems, or under 2 years of age who were born prematurely) are particularly prone to becoming more unwell from bacterial infections if they get flu. We would like to find out whether giving an antibiotic called coamoxiclav to “at risk” children (between 6 months and 12 years of age) within 5 days of them becoming ill with flu or flulike illness might: 1. Help stop them from developing bacterial infections and becoming more unwell. 2. Help them get better more quickly. 3. Affect how well antibiotics work against similar infections in future. The National Institute for Health Research (NIHR) is funding our research. We hope to recruit participants from general practices, across Thames Valley, Liverpool, Bristol and Southampton regions. In each region we will also aim to include recruitment from at least one outof hours centre and one accident and emergency department. Participant recruitment will be done by a healthcare professional appropriately trained in the study procedures and GCP. They will gain consent for each child to take part in the study from a parent or guardian. The healthcare professional will then record some details about the child’s flulike illness. A nose swab and, if possible, a throat swab will be taken from each child. Each child will be allocated a bottle of study medication, which may contain the antibiotic (coamoxiclav) or a placebo. Parents and guardians will be asked to give children one dose of medication twice a day for five days and to fill in a study diary. Parents and guardians will be asked if they would be willing for their child to have further optional throat swabs after three months, six months and twelve months.

Inclusion criteria:
· Aged 6 months to 12 years inclusive. · In `at risk’ category*. · Presenting with influenzalike illness (i.e. cough and fever**) during influenza season. · Presenting within 5 days of symptom onset. · Permanently registered at a general practice in England. · Parent /guardian able to complete study diary and questionnaires. Notes: *’At risk’ categories: The following `at risk’ categories are intended to guide clinicians in identifying which children are likely to be at greater risk of influenzarelated clinical deterioration or complications. However, healthcare professionals should also use their own clinical judgement to identify `at risk’ children and may discuss children whom they think may be `at risk’ with a medically qualified member of the research team. Respiratory · Asthma requiring continuous or repeated use of controller therapy (e.g. inhaled steroids, leukotriene receptor antagonists, longacting beta agonists, systemic steroids) · Admitted to hospital with exacerbation of asthma within the last 12 months. · Admitted to hospital with bronchiolitis within the last 12 months. · Recurrent viral wheeze (3 or more episodes within the last 12 months). · Bronchopulmonary dysplasia. Cardiac · Congenital heart disease being actively managed or monitored by cardiology team. · Chronic heart failure being actively managed or monitored by cardiology team. Neurological · Chronic neurological or neuromuscular disorder which compromises respiratory function (e.g. cerebral palsy). Renal · Chronic kidney disease defined as either of the following: · Impaired eGFR (estimated glomerular filtration rate) measurement within the last 12 months. · Known hereditary or structural kidney abnormality with or without impairment in eGFR. · Nephrotic syndrome. · Kidney transplantation. Liver · Cirrhosis · Biliary atresia · Chronic hepatitis Immunodeficiency · Asplenia or splenic dysfunction. · HIV infection. · Undergoing chemotherapy leading to immunosuppression. · Taking systemic steroids at a dose equivalent to prednisolone 20mg or more per day (any age) or >=1mg per kg per day (children under 20kg). Other · Diabetes mellitus (type 1 or type 2) or other metabolic condition. · Genetic abnormality (e.g. Down’s syndrome) · Sickle cell disease · Malignancy · Prematurity (born before 37 weeks gestation) in children aged 6 to 23 months. Impaired eGFR is defined as an eGFR measurement of 59 ml/min/1.73m2 or less within the last 12 months before study entry. However, to enter the trial the following two conditions must also be satisfied: 1) eGFR >=30 ml/min/1.73m2 based on most recent measurement within the last 12 months 2) no reason to suspect further deterioration in eGFR at time of study entry. Children with mild or moderate liver disease may enter the trial. Children with severe liver disease may not enter the trial. Severe liver disease is defined as hepatic impairment associated with any of the following: jaundice, impaired coagulation/increased bleeding risk, bilirubin persistently greater than 50 micromol/litre (two measurements within last 12 months). **Fever will be defined as any of the following: childreported fever, parentreported fever or temperature >37.8°C (axillary or tympanic temperature measurement).

Exclusion criteria:
· Known contraindication to coamoxiclav. · Child given antibiotics within the last 72 hours. · Child requires immediate antibiotics or hospital admission (clinician’s judgement). · Presence of any reason to prevent healthcare professional from obtaining high nasal swab. · Child with known cystic fibrosis. · Child previously entered into the ARCHIE study. · Child has been involved in another medicinal trial within the last 90 days.

Principal Investigator for this trial: Dr Louise Wells

Research Ethics Committee Reference: 13/NW/0621

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

EORTC 26091: Randomised trial assessing the significance of Bevacizumab in recurrent grade II and Grade III gliomas. The TAVAREC trial.

Summary:
Though low grade gliomas have a reasonable prognosis (years) when they recur, especially if they enhance with IV contrast (a sign of aggressive tumour behaviour), the outlook is poor with a median survival of less than 12 months. It is therefore important to find better treatments for this group of patients. The standard treatment is palliative chemotherapy, with temozolomide the most commonly used agent. Bevacizumab is an agent which affects the blood supply to tumours. Tumours which enhance with IV contrast have new blood vessels which are a potential target for bevacizumab. Bevacizumab is licenced for use in a number of tumour sites e.g. colorectal and lung cancer. It has also been used in high grade glioma but there is no randomised evidence. This international EU study’s aim is to see if the addition of bevacizumab to standard treatment can improve the survival of patients with recurrent low grade glioma

Inclusion criteria:
 Histologically proven grade II or grade III astrocytoma, oligodendroglioma or oligoastrocytoma. Demonstrated absence of 1p/19q codeletion on local testing. Availability of tumor material for translational research projects First recurrence after initial treatment with either radiotherapy and/or chemotherapy. Enhancing recurrence on MRI scan. Absence of any cardiovascular disorder. Absence of any thrombotic or hemorrhagic issue. Absence of known hypersensitivity. No underlying or previous conditions that could interfere with treatment. Normal hematological functions. Normal liver function. Normal renal function. Age 18 years. WHO Performance status 0 2. Able to give informed consent Women of childbearing potential (WOCBP) and men with partners of childbearing potential must be using an adequate method of contraception Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Informed consent should also be given for biological material to be stored and used for future research on brain tumors.

Exclusion criteria:
 More than one line of chemotherapy. Radiotherapy within the three months prior to the diagnosis of progression. Radiotherapy with a dose over 65 Gy, stereotactic radiosurgery or brachytherapy unless the recurrence is histologically proven. Prior treatment with Bevacizumab or other VEGF inhibitors or VEGFReceptor signaling inhibitors Invasive procedures within 4 weeks prior to randomization.

Principal Investigator for this trial: Dr Karen Foweraker

Research Ethics Committee Reference: 11/MRE00/1

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

R&I Contact Details

Contact information for the Research and Innovation team is detailed below.
Our postal address is:
Research & Innovation
Nottingham University Hospitals NHS Trust
Nottingham Integrated Clinical Research Centre
C Floor, South Block
Queen’s Medical Centre Campus
Derby Road Nottingham NG7 2UH
For general enquiries please email … Continue reading

Genetics of EGFR Mutation (GEM): A translational study of the EORTC lung group

Summary:
This is a prospective translational research study. The purpose of this study is to identify genetic factors that increase the risk of developing Epidermal Growth Factor Receptor (EGFR) mutant lung cancer and to see whether these factors influence lung cancer outcome. In particular we are looking to identify segments of lung cancer genetic code (DNA) that increases the risk of developing of two specific types of nonsmall cell lung cancer (NSCLC): NSCLC where the tumor has a mutation in a gene called EGFR (usually this is tested routinely in your hospital) ‘EGFR mutant lung cancer’ NSCLC where this mutation in EGFR is not found but patients have never smoked (less than 100 cigarettes in lifetime) or have previously only smoked very lightly (stopped smoking more than 1 year ago and smoked less than 10 packyears). For reasons that are currently unclear, these ‘EGFR mutant’ cancers are more frequently seen in the type of NSCLC called adenocarcinoma. They tend to occur more frequently in women, and are seen more frequently in patients of East Asian (e.g. Chinese) ethnic origin. The reasons why these cancers occur more frequently in these individuals than in the general population are unknown. About 2000 participants will take part in this study. Half of these patients will have NSCLC with a mutation in the EGFR gene, while the other half will have NSCLC without mutations in that gene and at the same time be never smoker (less than 100 cigarettes in lifetime) or exlight smoker (stopped smoking more than 1 year ago and smoked less than 10 packyears). A blood sample will be taken from each participant for analysis. Relevant medical history and demographic information will be collected. Participants will also be asked to complete a lifestyle questionnaire.

Inclusion criteria:
 Histologically or cytologicaly diagnosed NSCLC, all histologies are acceptable. Patients can be included in the study with any disease stage and at any time during the disease course. Any type (surgery, RT, chemotherapy, targeted agents) of previous treatment and any line of treatment are eligible. Age 18 years. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol those conditions should be discussed with the patient before registration in the trial Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations. Case Cohort: Patients with proven EGFR mutation in exons 1821 from tumor material (either primary tumor or metastasis). No known somatic KRAS, HER2, LKB1, BRAF, or PI3K, mutation or ALK gene rearrangement (or ALK3+ immunohistochemistry). If these mutations are known to be present the patient will be ineligible. However, patients will not be tested specifically for these mutations for this study and patients with unknown status are acceptable. If patients are subsequently tested after enrollment and found to harbor any of these mutations they will be considered ineligible and will be replaced. No known Li Fraumeni, Li Fraumenilike, or Peutz Jeghers syndrome family, or known germline carriers of mutant LKB1 or TP53. Patients will not have to be tested specifically for these syndromes to be eligible for this study. Control Cohort: Patients known to be somatic EGFR “wildtype,” i.e. no mutation detected in exons 1821 from tumor material. Never smoker (Exclusion criteria:
 Patients with unknown or failed tumor EGFR genotyping will be ineligible. Patients subsequently undergoing re genotyping which demonstrates an EGFR mutation will become eligible for the “case” cohort. Patients subsequently undergoing regenotyping which demonstrates an EGFR wildtype will become eligible for the “control” cohort.

Principal Investigator for this trial: Dr Ivo Hennig

Research Ethics Committee Reference: 14/YH/0062

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

Adjuvant peginterferonalpha-2b for 2 years vs Observation in patients with an ulcerated primary cutaneous melanoma with T(2-4)bN0M0: a randomised phase III trial of the EORTC Melanoma Group.

Summary:
Patients with stage II primary melanoma generally have a good prognosis after resection. However, once melanoma metastasizes beyond regional lymphnodes, the median survival is approximately 7 months. Ulceration is defined as the absence of intact skin covering a major portion of the primary melanoma based on microscopic examination. Survival rates of patients with an ulcerated melanoma are proportionally lower than those of patients with equivalent categorisation, but nonulcerated, melanoma. In patients with localized melanoma, tumour thickness, mitotic rate and ulceration are the most dominant prognostic factors. Interferon (IFN) alfa 2b is the most investigated agent for adjuvant treatment of patients with melanoma that are high risk of recurrence after definitive surgery. It has demonstrated consistent effects on overall survival (OS) compared with observation alone, and demonstrated low and intermediatedose regimens are more tolerable for longer periods of time it has produced transient improvements in recurrencefree survival or distant metastasesfree survival. However, no trial has indicated the optimum dose and duration for adjuvant interferon alfa in these highrisk melanoma patients. One EORTC trial suggested that longer duration of treatment with lower doses may be more effective than shorterterm therapy at higher doses. In previous EORTC trials, patients with ulcerated primaries have a greater benefit from IFN than nonulcerated primaries. This indicates that IFNadjuvant therapy might be sufficiently effective in ulcerated melanoma to become standard care. This means that after almost 20 years of IFN trials we might identify the patient subpopulation that significantly benefits not only at the recurrencefree survival level but also at the OS level. The consistency of these observations is striking and justifies a Randomized Clinical Trial to address the question of efficacy, toxicity and quality of life with peginterferon alfa2b as compared to observation after adequate surgery for ulcerated primary cutaneous melanomas.

Inclusion criteria:
 Subjects must have histologically documented ulcerated primary cutaneous melanoma with a Breslow thickness > 1mm that has been excised radically 3 months prior to randomization. Excision margins of at least 1 cm are required. In the head and neck areas and in case of locations distally on extremities narrower margins are acceptable as long as they are radical. In case subjects have undergone Sentinel Node staging after the excision of the primary, this must be done within the time frame of 3 months between the date of final excision of the primary and the date of randomization. Subjects must have an ECOG performance status of 0 or 1. Subjects must be between 1870 years old. Subjects must have adequate hepatic, renal and bone marrow function as defined by the following parameters obtained within 4 weeks prior to initiation of study treatment Subject must give informed consent according to ICHGCP or national/local policy

Exclusion criteria:
 Subjects suffering from a mucous membrane melanoma or ocular melanoma Subjects who have evidence of (non)regional lymph node metastases or intransit metastases (even if they have been resected) Subjects whose disease cannot be completely surgically resected Subjects who have not recovered from the effects of recent surgery Subjects with a history of prior malignancy within the past 10 years other than surgically cured nonmelanoma skin cancer or cervical carcinoma in situ Subjects who have severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease Subjects with thyroid dysfunction not responsive to therapy Subjects with uncontrolled diabetes mellitus Subjects suffering from an active autoimmune disease Subjects with active and/or uncontrolled infection, including active hepatitis Subjects who have a history of seropositivity for HIV Subjects who have a history of neuropsychiatric disorder requiring hospitalization Subjects who are known to be actively abusing alcohol or drugs Subjects who are pregnant, lactating, or of reproductive potential and not practicing an effective means of contraception Subjects with a medical condition requiring chronic systemic corticosteroids Subjects who have received any experimental therapy within 30 days prior to randomization in this study Subjects who have received any prior chemotherapy, immunotherapy, hormonal or radiation therapy for melanoma Subjects who have previously received interferonalpha for any reason Subject having history of epilepsy or other major central nervous system disease Subject having eyes disorders

Principal Investigator for this trial: Professor Poulam Patel

Research Ethics Committee Reference: 13/YH/0159

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

Standards, Procedures and Guidance

Our current standard operating procedures, regulatory standards, guidance documents, templates and forms are regularly updated please ensure that you are using the most current version.
If you need further assistance then please contact our QA/GCP Auditor Melanie Boulter.

Vacancy: Senior Research Manager (Regulatory Compliance & Award Management)

NUH Research & Innovation has a vacancy for a Senior Research Manager to lead on Regulatory Compliance & Award management.

Forthcoming MHRA inspection at Nottingham University Hospitals NHS Trust

The MHRA GCP Inspectorate is due to inspect NUH. The Trust was notified in February 2013 that an inspection is due to take place but as yet, the date and agenda of the inspection has not been confirmed. Continue reading

New Clinical Trials Toolkit uses tube map concept to guide researchers

NIHR has launched a new Clinical Trials Toolkit which is based on the design of a tube map. The clickable diagram differentiates between legal and good practice requirements, providing essential information at the ‘stations’ along the route

A phase III Trial of prophylactic irradiation of tracts in patients with Malignant Pleural Mesolthelioma following Invasive Chest Wall Intervention

Summary:
Mesothelioma is a cancer affecting the protective lining that covers many of the body’s internal organs. The most commonly affected sites are the lungs and internal chest wall. In the UK over 2300 patients are diagnosed with mesothelioma each year with numbers increasing annually. As part of diagnosis and treatment, mesothelioma patients undergo a procedure involving inserting a thin tube into the chest wall enabling an internal examination and for biopsies to be taken. This procedure can result in the development of tumours along the tract created. To try to reduce the risk of these tumours developing radiotherapy can be administered to the tract site following the procedure, a practice known as prophylactic irradiation of tracts (PIT). This is usually given before any chemotherapy. Mesothelioma patients have a poor prognosis. Treatment with PIT means that they may have to make up to 6 additional hospital visits. However, it is unclear whether PIT is helpful or necessary in this situation, with only 3 small studies with conflicting results, published to date. Even with such limited evidence, 70% of UK radiotherapy centres currently offer PIT. This study aims to establish whether PIT offers any benefit to patients. If PIT is proven to be ineffective, it will ensure that patients are no longer given unnecessary treatment and are not subjected to extra hospital visits. However, if PIT is shown to be beneficial, all patients will be offered the best effective treatment. Patients who participate in this trial will be randomised to receive either PIT or no PIT. Carefully monitored throughout, patients will be followedup to determine how often tumours develop on the chest wall, the benefits (if any) of giving PIT and any side effects that may occur from the treatment and whether tract metastases are painful when they occur.

Inclusion criteria:
· Either sex, age 18 years. · Diagnosis of mesothelioma by MDT · All histological subtypes. Where the histological diagnosis is unclear, a specialist thoracic pathologist should be consulted. · ECOG performance status 02. · Inoperable disease or operable disease in patients unsuitable for surgery as decided by a MDT. · Chest wall intervention with videoassisted thoracoscopy (VATS), open surgical biopsy, local anaesthetic thoracoscopy or chest drain. · Able to start radiotherapy within 42 days (6 weeks) from most recent chest wall intervention. · Chest wall intervention scar visible at time of randomisation. · No indwelling pleural catheters insitu at the intervention site · RT target volume acceptable by the local radiotherapist. · No previous open thoracotomy. · No previous radiotherapy to the region of the chest wall intervention site. · Not currently receiving chemotherapy and not received chemotherapy for mesothelioma before randomisation · No other previous or concomitant illness or treatment which in the opinion of the clinician will interfere with the trial treatments or comparisons. · Patients enrolled on other clinical trials could be considered after discussion with the chief investigators. · Female patients must satisfy the investigator that they are not pregnant, or are not of childbearing potential, or are using adequate contraception. · Patients must not be breastfeeding · Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and followup schedule those conditions should be discussed with the patient before registration in the trial · Before patient registration/randomisation, written informed consent must be given according to ICH/GCP, and national/local regulations. · Patients can only be randomised in this trial once.

Exclusion criteria:
· Patients who underwent a thoracotomy (as large thoracotomy scars may not be adequately covered by this radiotherapy technique) · Previous radiotherapy to the region of the chest wall intervention site · Patients currently receiving chemotherapy

Principal Investigator for this trial: Dr Sally Ann Morgan

Research Ethics Committee Reference: 12/NW/0249

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 randomised study of preoperative radiotherapy plus surgery versus surgery alone for patients with Retroperitoneal sarcoma (RPS).

Summary:
The long term outcome for patient with retroperitoneal sarcomas is poor. The major event leading to the poor outcome is local recurrence in the abdomen. The main objective of this study is to assess whether preoperative radiotherapy, as an adjunct to curativeintent surgery, improves the prognosis of patients with retroperitoneal sarcoma. This is a phase III multicentre randomised study to assess whether there is a difference in abdominal recurrencefree survival between retroperitoneal sarcoma patients undergoing curativeintent surgery alone and those undergoing preoperative radiotherapy followed by curativeintent surgery. It will further assess whether there is a difference in metastasisfree survival, abdominal recurrencefree interval and overall survival between patients undergoing curativeintent surgery alone and those undergoing preoperative radiotherapy followed by curative intent surgery. It will also assess the tumour response in patients undergoing preoperative radiotherapy and the toxicity of preoperative radiotherapy given prior to curative intent surgery in patients with retroperitoneal sarcoma. Patients older than 18 years, with an operable primary unifocal soft tissue sarcoma of retroperitoneal space or infraperitoneal spaces of pelvis will be eligible for this study. The study will be conducted at 8 major sarcoma centers across the UK and in several European countries. Over 39 months, 256 patients will be entered into the trial. Half of the patients will undergo preoperative radiotherapy followed by standard curativeintent surgery, while the other half of the patients will undergo standard curativeintent surgery alone. After completion of the study treatment, patients will be seen regularly at the treatment hospital for clinical examination and scans in order to assess of side effects and the status of the disease.

Inclusion criteria:
Tumourrelated criteria: Primary soft tissue sarcoma of retroperitoneal space or infraperitoneal spaces of pelvis Sarcoma not originated from bone structure, abdominal or gynecological viscera Unifocal tumor (not multifocal disease) Absence of extension through the sciatic notch or across the diaphragm Histologicallyproven RPS (local pathologist/ imagingguided or surgical biopsy), excluding the following histological subtypes: Gastrointestinal stromal tumor (GIST) Rhabdomyosarcomas PNET or other small round blue cells sarcoma, osteosarcoma or chondrosarcoma aggressive fibromatosis sarcomatoid or metastatic carcinoma  Tumour not previously treated (no previous surgery excluding diagnosis biopsy, radiotherapy or systemic therapy) Tumour both operable and suitable for radiotherapy (This will be based on pretreatment CT scan/MRI and multidisciplinary consultation with surgeon, radiation oncologist and radiologist (anticipated macroscopically complete resection, R0/R1 resection) Patients for whom surgery is expected to be R2 on the CTscan before randomization are not eligible Patients must have American Society of Anesthesiologist (ASA) score 2 (see Appendix G) The criteria for nonresectability are: (i) involvement of superior mesenteric artery or (ii) involvement of aorta or (iii) involvement of bone No metastatic disease Patient must have radiologically measurable disease (RECIST 1.1), as confirmed by abdominopelvic CT (IV and PO contrast) or MRI (with IV contrast) within the 28 days prior to randomization Patientrelated criteria: 18 years old WHO performance status 2 (see Appendix C) Absence of history of bowel obstruction or mesenteric ischemia or severe chronic inflammatory bowel disease Normal renal function: Calculated creatinine clearance within normal value (calculated by CockcroftGault see Appendix E) Functional contralateral kidney to the side involved by the RPS as assessed by intravenous pyelogram (done during the baseline CTscan) or differential renal isotope scan Normal bone marrow and hepatic function: White Blood cells 2.5 x10 9 cells/L Platelets 80 x10 9 cells/L Total bilirubin Principal Investigator for this trial: Dr Claire Esler

Research Ethics Committee Reference: 11/LO/2024

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

HEAT (Helicobacter Eradication Aspirin Trial): Can eradication prevent ulcer bleeding?

In 2007 there were 12,864 hospital admissions in England for gastric duodenal or peptic ulcer haemorrhage. HEAT is a large scale outcomes study designed to see whether a one week course of H. pylori eradication reduces hospitalisation for ulcer bleeding in patients using aspirin. With funding from the NIHR HTA Programme, it is being led by the University of Nottingham, with recruiting centres across the UK. Continue reading

Nottingham Penthrox acute pain control trial opens the door to research in A&E

Support provided by the Comprehensive Clinical Research Network recently helped NUH overcome the challenges of A&E and become the top recruiting site in an acute pain study. NUH demonstrates how to successfully conduct a clinical trial in a difficult Emergency Department environment. Continue reading

Nottingham University Hospitals R&I Research Manager vacancy, applications close 17th February

Do you wish to make a difference to research in the NHS? An opportunity has arisen for a Research Manager to join the Research & Innovation Department at Nottingham University Hospitals (NUH) NHS Trust. As Research Manager you will be a key member of the NUH R&I department and will play an important role in supporting the implementation of the Trust’s Research Strategy. Continue reading

Training

Introduction to Good Clinical Practice (GCP) Training Course
NIHR deliver regular GCP training.
For further information on GCP Training please visit the NIHR Website.
To book a place, you will first need to register. Once you have registered you can then … Continue reading

R&I Team Profiles

Dr Brian Thomson
Director of Research
Dr Brian Thomson qualified in Medicine from the University of Edinburgh and trained in medicine in Edinburgh, London and Cambridge before being appointed an Associate Professor and Honorary Consultant Physician in Nottingham in 1997. Dr Thomson … Continue reading

Entries Open for Clinical Research Site of the Year 2011

The PharmaTimes has opened a new competition, the Clinical Research Site of the Year, which is jointly sponsored by the NIHR and the ABPI. A new category of the Clinical Researcher of the Year competition, it has been introduced in recognition of the importance to the UK’s global competitiveness that a clinical research site can make. Continue reading

Regulatory Standards

Below is a selection of links related to regulatory standards which are relevant to Healthcare research in the UK. If you cannot find what you are looking for then please contact us on 0115 9709049.

General

Research Governance Framework, 2nd ed

Legislation & … Continue reading

Life Sciences Industry

Commercial research is important to NUH as the driving force for the adoption and diffusion of innovation.

It is through this process that new treatments, devices or laboratory tests are studied and brought forward for use by patients and staff.
Nottingham … Continue reading

NUH R&D completes MHRA inspection successfully

The MHRA has completed a four day routine GCP inspection of systems and processes. This took place in the last week of February and we were notified at the close of the audit that there were no critical findings. A … Continue reading

NUH routine MHRA inspection in February

NUH will soon undergo a routine GCP systems inspection by the MHRA (Medicines and Healthcare Products Regulatory Agency). This will take place during the last week of February and is coordinated by the R&D
department. The investigators who will be … Continue reading

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