Study of Cobimetinib in Combination With Atezolizumab and Bevacizumab in Participants With Gastrointestinal and Other Tumors

Part of paid clinical trials in Aurora, Colorado.

Sponsor
Hoffmann-La Roche
Study ID
NCT02876224
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Atezolizumab — DRUG
    Atezolizumab 840 mg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.
  • Bevacizumab — DRUG
    Bevacizumab 5 mg/kg will be administered by IV infusion on Days 1 and 15 of each 28-day cycle.
  • Cobimetinib — DRUG
    Cobimetinib 60 mg or at dose determined during safety run-in phase will be administered orally once daily for 21 days of each 28-day cycle as specified in the arm descriptions.

Study Details

This is an open-label, multicenter, single-arm, two-stage, Phase Ib study designed to assess the safety, tolerability, and pharmacokinetics of oral cobimetinib with intravenous (IV) atezolizumab and bevacizumab in participants with metastatic colorectal cancer (mCRC) who have received and progressed on at least one prior line of therapy that contained a fluoropyrimidine and oxaliplatin or irinotecan. There are two stages in this study: Stage 1 (safety run-in phase) and Stage 2 (dose expansion phase with two cohorts, an expansion cohort and a biopsy cohort).

Key Dates

Start date
Sep 30, 2016
Status verified
Aug 2019
Primary completion
Jun 25, 2019
Completion
Jun 25, 2019

Study Design

Enrollment
51 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Cobimetinib + Bevacizumab + Atezolizumab (Stage 1: SRP)
    Stage 1 Safety Run-in Phase (SRP): Approximately 12 participants will receive cobimetinib 60 milligrams (mg) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 milligrams per kilogram (mg/kg) administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Upon determination of the safety and tolerability of the treatment regimen, the study will proceed to Stage 2: dose expansion phase. If the results from the safety run-in phase require dose reduction in cobimetinib, then an additional Stage 1 cohort will be opened. Treatment will continue until the participant has disease progression according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
  • Experimental: Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: BC)
    Stage 2 Biopsy Cohort (BC): Approximately 7 evaluable participants in the biopsy cohort in expansion phase will receive bevacizumab 5 mg/kg IV on Cycle 1 Days 1 and 15 (tumor biopsy on Cycle 1 Day 8) and cobimetinib (at dose determined during safety run-in phase) orally on Cycle 1 Day 15 to Cycle 2 Day 14 (tumor biopsy on Cycle 1 Day 22). From Cycle 2 onwards, participants will follow the same treatment regimen for bevacizumab and atezolizumab (optional tumor biopsy on Cycle 2 Day 22) as those in the safety run-in phase and expansion cohort, and for cobimetinib cycles start at Day 15 and will continue 21 days to Day 7 of next cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Biopsies must be collected before the initiation of cobimetinib and atezolizumab. Treatment will continue until disease progression according to RECIST v1.1, unacceptable toxicity, death, decision to withdraw, or pregnancy, whichever occurs first.
  • Experimental: Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: EC)
    Stage 2 Expansion Cohort (EC): Approximately 14 participants will receive cobimetinib (at dose determined during safety run-in phase) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 mg/kg administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Treatment will continue until the participant has disease progression according to RECIST v1.1, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.

Primary Outcome Measure

Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 12 months ]

Locations (4)

FacilityCityStateZIPSite coordinators
University Of ColoradoAuroraColorado80045-
Memorial Sloan-Kettering Cancer CenterNew YorkNew York10065-
Sarah Cannon Research Inst.NashvilleTennessee37203-
The University of Texas MD Anderson Cancer CenterHoustonTexas77030-4009-

Find similar trials in Aurora, CO

By condition
Colorectal cancer
By specialty
OncologyGI oncology
By research site
University Of Colorado· Aurora, COMemorial Sloan-Kettering Cancer Center· New York, NYSarah Cannon Research Inst.· Nashville, TNThe University of Texas MD Anderson Cancer Center· Houston, TX

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