E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MSI Positive Colorectal Cancer
MSI Negative Colorectal Cancer
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E.1.1.1 | Medical condition in easily understood language |
MSI Positive Colorectal Cancer
MSI Negative Colorectal Cancer
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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 | 16.1 |
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 purpose of this study is to examine if nivolumab alone or in combination with ipilimumab will demonstrate a meaningful objective response rate in patients with recurrent and metastatic colon cancer who also have a specific biomarker in their tumors. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the IRRC objective response rate (ORR) of nivolumab monotherapy or nivolumab combined with ipilimumab in subjects with metastatic MSI-H CRC |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CA209142 will also contain a safety cohort of subjects with non-Microsatellite Instability-High Colorectal Cancer to assess the safety and tolerability of nivolumab in combination with ipilimumab in subjects with non-Microsatellite Instability-High Colorectal Cancer in preparation for an analogous 2 stage assessment of the response rate for the combination in Microsatellite Instability-High Colorectal Cancer. See also protocol, section 3.1 (same version and date as the protocol).
Approximately 10 subjects with recurrent or metastatic nMSI-H CRC will be randomized (1:1) to Dose Level 2a and Dose Level 2b. |
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E.3 | Principal inclusion criteria |
•Men and women ≥ 18 years of age
•ECOG performance status 0 to 1.
•Histologically confirmed colorectal cancer.
•Measurable disease by CT or MRI.
•Testing for MSI Status
•Adequate organ function as defined by study-specific laboratory tests
•Must use acceptable form of birth control throughout the study. After the final dose of study drug, an acceptable form of birth control must be used for 23 weeks for women of childbearing potential (WOCBP) and 31 weeks for men who are sexually active with WOCBP.
•Signed informed consent
•Willing and able to comply with study procedures |
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E.4 | Principal exclusion criteria |
•Active brain metastases or leptomeningeal metastases are not allowed.
•Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
•Prior malignancy active within the previous 3 years except for locally curable cancers
•Subjects with active, known or suspected autoimmune disease.
•Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of study drug administration. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is objective response rate (ORR) in all MSI-H subjects as determined by investigators.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject’s first dose of study therapy. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint is ORR in all MSI-H subjects based on IRRC determination. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The final analysis of the secondary endpoint will occur at the time of the primary endpoint analysis.
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker Assessments, Outcomes Research Assessments |
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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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Ireland |
Italy |
Australia |
Spain |
United States |
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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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Last follow-up visit of the Last Subject |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 20 |