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An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread

NCT02060188

Description:

The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: An Investigational Immuno-therapy Study of Nivolumab, and Nivolumab in Combination With Other Anti-cancer Drugs, in Colon Cancer That Has Come Back or Has Spread
  • Official Title: A Phase 2 Clinical Trial of Nivolumab, or Nivolumab Combinations in Recurrent and Metastatic Microsatellite High (MSI-H) and Non-MSI-H Colon Cancer

Clinical Trial IDs

  • ORG STUDY ID: CA209-142
  • SECONDARY ID: 2013-003939-30
  • NCT ID: NCT02060188

Conditions

  • Microsatellite Unstable Colorectal Cancer
  • Microsatellite Stable Colorectal Cancer
  • Mismatch Repair Proficient Colorectal Cancer
  • Mismatch Repair Deficient Colorectal Cancer

Interventions

DrugSynonymsArms
IpilimumabYervoyNivolumab (Nivo) + Ipilimumab (Ipi)
NivolumabBMS-936558, OpdivoNivolumab Monotherapy
CobimetinibCotellicNivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4
DaratumumabDarzalexNivolumab (Nivo) + Daratumumab Cohort C6
anti-LAG-3 antibodyBMS-986016Nivolumab (Nivo) + BMS-986016 Cohort C5

Purpose

The purpose of this study is to examine if Nivolumab by itself, or Nivolumab in combination with other anti-cancer drugs, will result in meaningful tumor size reduction, in patients with colon cancer that has come back or has spread, and who have a specific biomarker in their tumors.

Detailed Description

      Allocation: The Microsatellite Instability High (MSI-High) and C4 and C6 Cohort Parts of the
      trial are Non-randomized, The Non-MSI high Dose Escalation Phase part of the trial contained
      a randomized portion
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab MonotherapyExperimentalNivolumab administered as IV infusion at a dose of 3mg/kg every 2 weeks until disease progression
  • Nivolumab
Nivolumab (Nivo) + Ipilimumab (Ipi)ExperimentalNivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3 week (wk) for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression Dose Escalation Phase: (Complete) Dose Level (DL) 1: Nivo 0.3mg/Kg with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression DL 1: Nivo 1mg/Kg IV with Ipi 1 mg/Kg IV every 3 wk for 4 doses followed by Nivo 3mg/Kg IV every 2wk until progression DL 2a: Nivo 1mg/Kg IV with Ipi 3 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression DL 2b: Nivo 3mg/Kg IV with Ipi 1 mg/Kg IV every 3wk for 4 doses followed by Nivo 3mg/Kg IV every 2 wk until progression
  • Ipilimumab
  • Nivolumab
Nivolumab (Nivo) + Ipilimumab (Ipi) Cohort C3ExperimentalNivo IV dosed every 2wk with Ipi IV dosed every 6wk.
  • Ipilimumab
  • Nivolumab
Nivolumab (Nivo) + Ipilimumab (Ipi) + Cobimetinib Cohort C4ExperimentalNivo IV dosed every 2wk, with Ipi IV dosed every 6wk, combined with Cobimetinib dosed orally once daily 21 days on/7 days off.
  • Ipilimumab
  • Nivolumab
  • Cobimetinib
Nivolumab (Nivo) + BMS-986016 Cohort C5ExperimentalNivo IV dosed every 2wk with BMS-986016 dosed every 2 wk
  • Nivolumab
  • anti-LAG-3 antibody
Nivolumab (Nivo) + Daratumumab Cohort C6ExperimentalDaratumumab IV dosed weekly for week 1-8; then every 2 wks from Week 9-24; then every 4 wks on week 25; with Nivo dosed every 2 wks starting at week 3 and every 4 wks starting at week 25
  • Nivolumab
  • Daratumumab

Eligibility Criteria

        For more information regarding BMS clinical trial participation, please visit
        www.BMSStudyConnect.com

        Inclusion Criteria:

          -  Men and women ≥ 18 years of age

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          -  Histologically confirmed recurrent or metastatic colorectal cancer

          -  Measurable disease by CT or MRI

          -  Testing for MSI Status (by an accredited lab)

               1. Subjects with microsatellite instability high (MSI-H) tumors will enroll in the
                  MSI-H Cohort (mStage and cStage groups), the C3 Cohort, and the C5 Cohort.

               2. Subjects with phenotypes that are non-microsatellite instability high (non-MSI-H)
                  will enroll in the non- MSI-H Safety Cohort and the C6, C4 Cohorts.

          -  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

          -  Subjects enrolled into the C3 Cohort must have not had treatment for their metastatic
             disease

        Exclusion Criteria:

          -  Active brain metastases or leptomeningeal metastases are not allowed.

          -  Prior treatment with an anti-Programmed Death Receptor (PD)-1, anti-PD-L1, anti-PD-L2,
             anti-Cytotoxic T-Cell Lymphoma-4 Antigen (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

        Other protocol defined inclusion/exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) in all MSI-High and non-MSI-High subjects as determined by Investigators
Time Frame:The final analysis of the primary endpoint will occur at least 6 months after the last enrolled subject's first dose of study therapy (Approximately up to 34 months)
Safety Issue:
Description:(Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later)) (Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/-1 wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued (whichever occurs later))

Secondary Outcome Measures

Measure:ORR in all MSI-H and non-MSI-H subjects based on IRRC determination
Time Frame:The final analysis of the secondary endpoint will occur the time of the primary endpoint analysis (Approximately up to 34 months)
Safety Issue:
Description:Tumor imaging assessments will occur every 6 weeks from the date of first dose (+/- wk) for the first 24 weeks, then every 12 wks (+/- 1 wk) thereafter until disease progression or treatment is discontinued(whichever occurs later)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bristol-Myers Squibb

Last Updated

February 22, 2018