E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061451 |
E.1.2 | Term | Colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this trial is To detect the rate of durable clinical benefit in patients with strong class II expressing Micro Satellite Stable Colorectacl Cancer treated with single agent nivolumab, to justify further investigation in subsequent studies. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to evaluate the benefit to patients in terms of other clinical outcomes, to include: • Objective response rate • Best percentage change in sum of target lesion diameters • Time to maximal response • Progression free survival time • Overall survival time
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically confirmed locally advanced or metastatic MSS CRC with strong class II expression (greater than 50% cancer cell positivity for class II expression on immunohistochemistry). • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 • 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 uni-dimensionally measurable disease as per RECIST version 1.1 • Demonstrate adequate haematological function: o Platelet count ≥100 x 109 /L o Neutrophils ≥1.5 x 109/L o Haemoglobin ≥ 90 g/L • Demonstrate adequate hepatic function: o Serum bilirubin ≤1.5 x upper limit of normal (ULN) o Serum AST or ALT ≤2.5 x ULN or <5 x ULN in the presence of liver metastases • 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). • Patients must agree to the use of contraception
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E.4 | Principal exclusion criteria |
• Previous treatment with PD1/PDL1 inhibitors. • Untreated symptomatic brain or leptomeningeal metastatic disease. • Medical or psychiatric conditions compromising informed consent. • Any medical condition which, in the opinion of the Investigator, would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol. • Administration of chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of trial therapy • Patient has not recovered to CTCAE grade 1 or better from the Adverse Event (AE) due to cancer therapeutics administered more than 4 weeks earlier. • Active autoimmune disease that has required systemic treatment in past 2 years (i.e. 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. • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 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. • Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis). • Patient has a known history of other malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years. • Has a history of non-infectious pneumonitis requiring steroids or has active neumonitis or significantly reduced transfer coefficient (KCO). • Female patients that are either pregnant or breast feeding. • Male and female patients (of childbearing age) not willing to use adequate contraception. • Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody. • Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing. • Known history of tuberculosis. • Patient has an active infection requiring therapy. • Has received a live vaccine within 30 days prior to the first dose of trial treatment. • Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
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E.5 End points |
E.5.1 | Primary end point(s) |
Durable clinical benefit (DCB defined as the occurrence of complete response (CR), partial response (PR) or stable disease (SD) for 27 weeks or greater. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will have CT scans every 9 weeks from baseline up to 45 weeks treatment, then every 12 weeks thereafter until disease progression. On each occasion, overall tumour burden will be assessed using RECIST version 1.1. |
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E.5.2 | Secondary end point(s) |
Objective response: Objective response (OR) is the occurrence of CR or PR as the best overall response. OR will be based on responses confirmed using the subsequent 9-weekly scan but OR based on unconfirmed responses will also be reported.
Progression-free survival time: This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression. Patients who are alive with no recorded progression at the time of analysis will be censored at the date of the CT scan when they were last recorded with an evaluable measure that was not progression.
Overall survival time: This is defined as the time from commencement of trial treatment to the date of death. Patients who are alive at the time of analysis will be censored at the date last seen alive. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Patients will have CT scans every 8 weeks from baseline up to 10 months treatment then every 12 weeks thereafter until disease progression. On each occasion, overall tumour burden will be assessed using RECIST version 1.1.
Patient's will be followed up for survival post treatment discontinuation every four weeks for six months then 12 weekly thereafter up to five years. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of trial will be 6 months after the last data capture. This will allow sufficient time for the completion of protocol procedures, data collection and data input. The Trial Office will notify the MHRA and main REC that the trial has ended and will provide them with a summary of the clinical trial report within 12 months of the end of trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |