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About
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with class II expressing microsatellite stable colorectal cancer.
Full description
Immuno-oncology is transforming the care of certain patients with cancer. Not all patients respond to these therapies however, and in some common cancers checkpoint blockade has failed to make any real impact. In 2014 there were over 41,000 new cases of colorectal cancer (CRC) in the UK and nearly 16,000 deaths from the disease, making it the second commonest cause of cancer death (Cancer Research UK Cancer Statistics Key Facts). 15% of patients with CRC develop it as a result of deficient mismatch repair (microsatellite instability - MSI): this cohort of patients respond well to PD-1/PD-L1 blockade as these tumours harbour a very high number of mutations thus increasing the likelihood of the presence of immunogenic neo-epitopes which elicit an immune response1. The majority of CRC patients, particularly those with metastatic disease (around 95%), do not display this hyper-mutator phenotype (microsatellite stable (MSS) CRC) and in these patients the results of PD-1/PD-L1 blockade have been disappointing.
In summary, MSS CRC patients with a class II expression appear to represent immunologically a group of MSI-like MSS patients that may respond to usefully to the immunotherapy agent nivolumab as a single agent and thus a trial of nivolumab in patients with class II expression of their cancer cells appears to be highly justified.
Enrollment
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Inclusion criteria
Histologically confirmed locally advanced or metastatic MSS CRC with class II expression (greater than 1% cancer cell positivity for class II expression on immunohistochemistry).
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (APPENDIX 1)
Age ≥ 18 years
Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. Trial treatment as first line therapy is permitted if the patient has declined standard of care therapy.
CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating unidimensionally measurable disease as per RECIST version 1.1 (APPENDIX 3).
Demonstrate adequate haematological function:
Demonstrate adequate hepatic function:
Demonstrate adequate renal function
o Creatinine clearance <1.5 times ULN and >30ml/min (as per institutional standard).
Provision of signed and dated, written informed consent prior to any trial specific procedures, sampling and analyses.
Negative pregnancy test (female patients of reproductive potential). (Serum Test must be negative)
Patients must agree to the use of contraception as detailed in section 7.8
Exclusion criteria
Previous treatment with PD1/PDL1 inhibitors.
with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Primary purpose
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Interventional model
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35 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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