Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies

Part of paid clinical trials in New York, New York.

Sponsor
Columbia University
Study ID
NCT04214418
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

  • Gastrointestinal Cancer

Eligibility Criteria

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

Interventions

  • Cobimetinib — DRUG
    (40-60 mg) orally once daily (morning) on days 1-21 of each 28-day selective small molecule inhibitor for MEK1 and MEK2
  • Hydroxychloroquine — DRUG
    (600mg) orally twice daily on days 1-28 of each 28-day cycle
  • Atezolizumab — DRUG
    840 mg IV on Days 1 and 15 of each cycle humanized IgG1 monoclonal antibody (MAb)

Study Details

This research study is for patients with an advanced cancer that carries a mutation in a gene called KRAS. Genes are parts of our DNA which carry instructions for a cell (the smallest component of an body part). In many cancers, the KRAS gene contains errors (mutations) which allows the tumors to grow. The purpose of this study is to determine if combination treatment with atezolizumab, cobimetinib, and hydroxychloroquine is safe, and if it will decrease the size of the tumor and prolong life in patients whose tumors contain this mutation. Cobimetinib and atezolizumab are both approved by the FDA for use in other cancers, but not in some cancer types being studied in this trial. Hydroxychloroquine is FDA approved to treat malaria and other conditions, but has also not been approved for these cancer types. Preliminary results have shown that this combination of drugs is effective at killing cancer cells and shrinking tumors in several KRAS-mutated cancers in animals.

Key Dates

Start date
Feb 12, 2020
Status verified
Nov 2024
Primary completion
Apr 11, 2022
Completion
Jul 1, 2022

Study Design

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

Arms

  • Experimental: Phase 1: Maximum Tolerated Dose (MTD)
    Subjects will be treated with combination therapy at the designated dose levels: Dose 1 - Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg, no Atezolizumab Dose 2 - Hydroxychloroquine 600mg twice per day, Cobimetinib 40mg, Atezolizumab 840mg Dose 3 - Hydroxychloroquine 600mg twice per day, Cobimetinib 60mg, Atezolizumab 840mg
  • Experimental: Phase 2: Cohort 1
    Advanced Pancreatic Adenocarcinoma (N = 23-67) subjects will receive study treatment based on the MTD determined from Phase 1
  • Experimental: Phase 2: Cohort 2
    Advanced Colorectal Adenocarcinoma (N = 20-34) subjects will receive study treatment based on the MTD determined from Phase 1
  • Experimental: Phase 2: Cohort 3
    Histology Agnostic Adenocarcinoma (N = 23-56) subjects will receive study treatment based on the MTD determined from Phase 1

Primary Outcome Measure

Phase 1: Estimated Maximum Tolerated Dose (MTD) Hydroxychloroquine (HCQ) [ Time Frame: 28 days ]

Locations (2)

FacilityCityStateZIPSite coordinators
Columbia University Irving Medical CenterNew YorkNew York10032-
Brown UniversityProvidenceRhode Island02912-

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Columbia University Irving Medical Center· New York, NYBrown University· Providence, RI

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