An Investigational Immuno-therapy Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Cancer of the Colon or Rectum That Has Spread
- Conditions
- Colorectal CancerColorectal NeoplasmColorectal TumorsColorectal Carcinoma
- Interventions
- Registration Number
- NCT03377361
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to investigate treatment with nivolumab in combination with trametinib with or without ipilimumab in participants with previously treated cancer of the colon or rectum that has spread.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 325
- Histologically or cytologically confirmed previously treated metastatic colorectal cancer with adenocarcinoma histology and in Stage IV per American Joint Committee on Cancer (version 4.0) at study entry
- Microsatellite status should be performed per local standard of practice, immunohistochemistry (IHC) and/or PCR. If IHC results are equivocal, PCR is required for determining microsatellite stable (MSS) status
- Must have measurable disease per RECIST 1.1. Participants with lesions in a previously irradiated field as the sole site of measurable disease will be permitted to enroll provided the lesion(s) have demonstrated clear progression and can be measured accurately
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 at screening and on cycle 1 day 1 (C1D1)
- BRAF V600 mutant colorectal cancer
- Active brain metastases or leptomeningeal metastases
- Active, known or suspected autoimmune disease
- Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration
- History of interstitial lung disease or pneumonitis
- Prior treatment with immune checkpoint inhibitors and mitogen-activated protein kinase enzymes (MEK) inhibitors
- History of allergy or hypersensitivity to study drug components
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib Nivolumab - Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib Nivolumab - Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib Ipilimumab - Part 1 Cohort 1 3rd Line (3L): nivolumab + trametinib Trametinib - Part 1A Cohort 2 2nd Line (2L): nivolumab + ipilimumab + trametinib Trametinib - Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib Trametinib - Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib Trametinib - Part 2 Cohort 5 (3L): Regorafenib Regorafenib - Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib Trametinib - Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib Nivolumab - Part 2 Cohort 4 (3L): nivolumab + ipilimumab + trametinib Ipilimumab - Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib Nivolumab - Part 1B Cohort 6 (2L): nivolumab + ipilimumab + trametinib Ipilimumab - Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib Nivolumab - Part 1A Cohort 3 (2L): nivolumab + ipilimumab + trametinib Ipilimumab -
- Primary Outcome Measures
Name Time Method Incidence of Deaths Up to 100 months Incidence of Serious Adverse Events (SAEs) Approximately 100 months Incidence of Adverse Events (AEs) Approximately 100 months Incidence of clinically significant changes in clinical laboratory results: Hematology tests Up to 77 months Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests Up to 77 months Objective response rate (ORR) by investigator (Part 1B and Part 2) Approximately 24 months Incidence of dose limiting toxicity (DLTs) Up to 23 months Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests Up to 77 months
- Secondary Outcome Measures
Name Time Method Disease control rate (DCR) Approximately 24 months Time to response (TTR) Approximately 24 months Incidence of Adverse Events (AEs) Approximately 100 months Incidence of Serious Adverse Events (SAEs) Approximately 100 months Objective response rate (ORR) (Part 1A and Part 1) Approximately 24 months Incidence of clinically significant changes in clinical laboratory results: Hematology tests Up to 77 months Duration of response (DOR) Approximately 24 months Progression-free survival (PFS) by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 Approximately 24 months Best overall response (BOR) Up to 24 months Overall survival (OS) Approximately 40 months Incidence of Deaths Up to 100 months Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests Up to 77 months Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests Up to 77 months
Trial Locations
- Locations (47)
Local Institution - 0111
🇺🇸Miami, Florida, United States
Local Institution - 0118
🇨🇱Santiago, Región Metropolitana De Santiago, Chile
Local Institution - 0002
🇺🇸Madison, Wisconsin, United States
Local Institution - 0003
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0107
🇺🇸Gainesville, Florida, United States
Local Institution - 0001
🇺🇸San Francisco, California, United States
Local Institution - 0027
🇺🇸Los Angeles, California, United States
Local Institution - 0022
🇺🇸Birmingham, Alabama, United States
Local Institution - 0067
🇺🇸Los Angeles, California, United States
Local Institution - 0028
🇺🇸Baltimore, Maryland, United States
Local Institution - 0116
🇺🇸Hattiesburg, Mississippi, United States
Local Institution - 0103
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0104
🇺🇸New York, New York, United States
Local Institution - 0029
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0100
🇺🇸Lancaster, Pennsylvania, United States
Thomas Jefferson University - Clinical Research Institute
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0101
🇺🇸Temple, Texas, United States
Local Institution - 0120
🇦🇷Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
Local Institution - 0123
🇦🇷Ciudad Autónoma de Buenos Aires, Distrito Federal, Argentina
Local Institution - 0044
🇦🇺Blacktown, New South Wales, Australia
Local Institution - 0055
🇦🇺Clayton, Victoria, Australia
Local Institution - 0043
🇦🇺Southport, Queensland, Australia
Local Institution - 0068
🇦🇺Elizabeth Vale, South Australia, Australia
Local Institution - 0069
🇦🇺Heidelberg, Victoria, Australia
Local Institution - 0113
🇨🇦Edmonton, Alberta, Canada
Local Institution
🇧🇪Woluwe-Saint-Lambert, Belgium
Local Institution - 0070
🇨🇦Toronto, Ontario, Canada
Local Institution - 0077
🇨🇦Montréal, Quebec, Canada
Local Institution - 0076
🇨🇦Ottawa, Canada
Local Institution - 0117
🇨🇱Santiago, Metropolitana, Chile
Local Institution - 0073
🇨🇿Hradec Kralove, Czechia
Local Institution - 0071
🇨🇿Brno, Czechia
Local Institution - 0004
🇩🇪Hannover, Germany
Local Institution - 0072
🇨🇿Olomouc, Olomoucký Kraj, Czechia
Local Institution - 0095
🇮🇹Catania, Italy
Local Institution - 0093
🇮🇹Milan, Italy
Local Institution - 0080
🇪🇸Pamplona, Navarra, Spain
Local Institution - 0079
🇪🇸Badalona, Barcelona [Barcelona], Spain
Local Institution - 0092
🇮🇹Padova, Italy
Local Institution - 0094
🇮🇹Rozzano, Italy
Local Institution - 0052
🇪🇸Barcelona, Spain
Local Institution - 0051
🇪🇸Madrid, Spain
Local Institution - 0115
🇪🇸Madrid, Spain
Local Institution - 0096
🇪🇸Sevilla, Spain
Local Institution - 0114
🇪🇸Madrid, Spain
Local Institution - 0122
🇦🇷Buenos Aires, Distrito Federal, Argentina
Local Institution - 0119
🇦🇷Buenos Aires, Argentina