Clinical trial NCT03377361: 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
Official title: A Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Participants With Previously Treated Metastatic Colorectal Cancers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Colorectal Cancer
Colorectal Tumors
Colorectal Carcinoma
Colorectal Neoplasm
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
Collaborators: name: Novartis
First posted: 2017-12-19
Enrollment: 325
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLTs)
timeFrame: Up to 23 months
measure: Incidence of Adverse Events (AEs)
timeFrame: Approximately 100 months
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Approximately 100 months
measure: Incidence of Deaths
timeFrame: Up to 100 months
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 77 months
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Up to 77 months
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 77 months
measure: Objective response rate (ORR) by investigator (Part 1B and Part 2)
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Objective response rate (ORR) (Part 1A and Part 1)
timeFrame: Approximately 24 months
measure: Disease control rate (DCR)
timeFrame: Approximately 24 months
measure: Duration of response (DOR)
timeFrame: Approximately 24 months
measure: Time to response (TTR)
timeFrame: Approximately 24 months
measure: Progression-free survival (PFS) by investigator per response evaluation criteria in solid tumors (RECIST) v1.1
timeFrame: Approximately 24 months
measure: Best overall response (BOR)
timeFrame: Up to 24 months
measure: Overall survival (OS)
timeFrame: Approximately 40 months
measure: Incidence of Adverse Events (AEs)
timeFrame: Approximately 100 months
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Approximately 100 months
measure: Incidence of Deaths
timeFrame: Up to 100 months
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 77 months
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Up to 77 months
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 77 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0022
state: Alabama
city: Los Angeles
country: United States
facility: Local Institution - 0027
state: California
city: Los Angeles
country: United States
facility: Local Institution - 0067
state: California
city: San Francisco
country: United States
facility: Local Institution - 0001
state: California
city: Gainesville
country: United States
facility: Local Institution - 0107
state: Florida
city: Miami
country: United States
facility: Local Institution - 0111
state: Florida
city: Baltimore
country: United States
facility: Local Institution - 0028
state: Maryland
city: Hattiesburg
country: United States
facility: Local Institution - 0116
state: Mississippi
city: Saint Louis
country: United States
facility: Local Institution - 0103
state: Missouri
city: New York
country: United States
facility: Local Institution - 0104
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0029
state: North Carolina
city: Lancaster
country: United States
facility: Local Institution - 0100
state: Pennsylvania
city: Philadelphia
country: United States
facility: Local Institution - 0003
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University - Clinical Research Institute
state: Pennsylvania
city: Temple
country: United States
facility: Local Institution - 0101
state: Texas
city: Madison
country: United States
facility: Local Institution - 0002
state: Wisconsin
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 0120
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0122
state: Distrito Federal
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Local Institution - 0123
state: Distrito Federal
city: Buenos Aires
country: Argentina
facility: Local Institution - 0119
city: Blacktown
country: Australia
facility: Local Institution - 0044
state: New South Wales
city: Southport
country: Australia
facility: Local Institution - 0043
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Local Institution - 0068
state: South Australia
city: Clayton
country: Australia
facility: Local Institution - 0055
state: Victoria
city: Heidelberg
country: Australia
facility: Local Institution - 0069
state: Victoria
city: Woluwe-Saint-Lambert
country: Belgium
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution - 0113
state: Alberta
city: Toronto
country: Canada
facility: Local Institution - 0070
state: Ontario
city: Montréal
country: Canada
facility: Local Institution - 0077
state: Quebec
city: Ottawa
country: Canada
facility: Local Institution - 0076
city: Santiago
country: Chile
facility: Local Institution - 0117
state: Metropolitana
city: Santiago
country: Chile
facility: Local Institution - 0118
state: Región Metropolitana De Santiago
city: Olomouc
country: Czechia
facility: Local Institution - 0072
state: Olomoucký Kraj
city: Brno
country: Czechia
facility: Local Institution - 0071
city: Hradec Kralove
country: Czechia
facility: Local Institution - 0073
city: Hannover
country: Germany
facility: Local Institution - 0004
city: Catania
country: Italy
facility: Local Institution - 0095
city: Milan
country: Italy
facility: Local Institution - 0093
city: Padova
country: Italy
facility: Local Institution - 0092
city: Rozzano
country: Italy
facility: Local Institution - 0094
city: Badalona
country: Spain
facility: Local Institution - 0079
state: Barcelona [Barcelona]
city: Pamplona
country: Spain
facility: Local Institution - 0080
state: Navarra
city: Barcelona
country: Spain
facility: Local Institution - 0052
city: Madrid
country: Spain
facility: Local Institution - 0114
city: Madrid
country: Spain
facility: Local Institution - 0051
city: Madrid
country: Spain
facility: Local Institution - 0115
city: Sevilla
country: Spain
facility: Local Institution - 0096
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: