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Protocol No. NRGGI004

Principal Investigator Mulkerin, Daniel

Phase III

Age Group Adult

Scope National

Sponsor Type National

Title Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab Combination Chemotherapy with or Without Atezolizumab or Atezolizumab

Objective
The purpose of this study is to learn if adding an experimental drug, atezolizumab (MPDL3280A), to a usual treatment or giving the experimental drug alone is better than the usual treatment alone. The usual treatment in this study is the chemotherapy drugs, 5-flouorouracil (5-FU), leucovorin, and oxaliplatin. This combination is called FOLFOX. In addition to FOLFOX, bevacizumab will be given. Bevacizumab is in a group of drugs called biologic therapy. FOLFOX and bevacizumab are approved by the FDA to treat metastatic CRC. To be better than FOLFOX and bevacizumab, atezolizumab given with FOLFOX and bevacizumab or atezolizumab given alone should keep your cancer from growing for more than 7 months
Another purpose of this study is to test the good and bad effects of atezolizumab when added to the usual treatment and when given alone. Atezolizumab may keep your cancer from growing but it can also cause side effects. Atezolizumab is FDA-approved for treating metastatic cancers of the bladder and lung. Atezolizumab is considered experimental in this study because it is not approved to treat metastatic CRC

Treatment This study has three study groups:
  • Group 1 will get FOLFOX and bevacizumab.
  • Group 2 will get atezolizumab alone.
  • Group 3 will receive FOLFOX and bevacizumab plus atezolizumab

  • Description Phase 3 mFOLFOX6/Bevacizumab, and/or Atezolizumab in treating patients with dMMR MCRC

    Key Eligibility
  • Must be 18 years of age or greater
  • ECOG Performance status of 0-2
  • Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer
  • Tumor determined to be mismatch-repair deficient (dMMR) by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6. Note: MSI-H diagnosed by MSI testing (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) is not eligible unless dMMR is confirmed by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers including MLH1, MSH2, PMS2 and MSH6
  • An adequate amount of archived tumor tissue, either from primary colorectal cancer site or metastatic lesions, for central confirmation of dMMR status: Either whole or part of the FFPE block containing tumor tissue; or at least 9 unstained slides containing tumor sections
  • Documentation by PET/CT scan, CT scan, or MRI that the patient has untreated measurable metastatic disease per RECIST 1.1
  • Adequate hematologic, hepatic and renal function
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)
  • Men with female partners of child-bearing potential must agree to use adequate contraception
    EXCLUSION
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin
  • Uncontrolled high blood pressure
  • Any of the following cardiac conditions: Documented NYHA Class III or IV congestive heart failure, Myocardial infarction within 6 months prior to randomization Unstable angina within 6 months prior to randomization, Symptomatic arrhythmia
  • Known DPD (dihydro pyrimidine dehydrogenase) deficiency
  • Symptomatic peripheral sensory neuropathy ≥ grade 2 in patients with no prior oxaliplatin therapy
  • Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents. Patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization, no history of severe immune-related adverse effect from antiCTLA-4
  • Pt's taking bisphosphonate therapy for symptomatic hypercalcemia
  • Patients requiring treatment with a RANKL inhibitor (e.g., denosumab) who cannot discontinue it before treatment with atezolizumab
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Patients positive for human immunodeficiency virus are NOT excluded from this study, but HIV-positive pt's must have: stable regimen of highly active anti-retroviral therapy, and No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections; CD4 count above 250 cells/µL and an undetectable HIV viral load on standard PCR tests

  • Applicable Disease Sites Colon and Rectum

    Status Open

    Participating Institutions Aspirus UW Cancer Center (formerly Riverview Hospital); Aspirus Wausau Hospital, Aspirus Regional Cancer Center; Langlade Memorial Hospital, Aspirus Regional Cancer Ctr; Mercy Health Systems, Janesville ; UW Hospital and Clinics; UWCCC 1 South Park