Colorectal Cancer Metastatic dMMR Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab Combination Chemotherapy with or without Atezolizumab or Atezolizumab Monotherapy in the First-Line Treatment of Patients with Deficient DNA Mismatch Repair (dMMR) Metastatic Colorectal Cancer

Purpose

To determine the efficacy, based on PFS, of mFOLFOX6/bevacizumab plus atezolizumab (combination) and atezolizumab (single agent) as compared to mFOLFOX6/bevacizumab.

Inclusion Criteria:

  • The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 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 Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; Note: microsatellite instability high (MSI-H) diagnosed by microsatellite instability (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 formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue; or
    • At least 9 unstained slides containing tumor sections
  • Documentation by positron emission tomography(PET)/computed tomography (CT) scan, CT scan, or magnetic resonance imaging (MRI) that the patient has untreated measurable metastatic disease per RECIST 1.1
  • No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
  • Absolute neutrophil count (ANC) must be >= 1500/mm^3 (obtained within 28 days prior randomization)
  • Platelet count must be >= 100,000/mm^3 (obtained within 28 days prior randomization)
  • Hemoglobin must be >= 8 g/dL (obtained within 28 days prior randomization)
  • Total bilirubin must be =< 1.5 x ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation > 1.5 x ULN to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin (obtained within 28 days prior randomization); and
  • Alkaline phosphatase must be =< 2.5 x ULN for the lab with the following exception: patients with documented liver metastases or bone involvement - alkaline phosphatase must be =< 5 x ULN (obtained within 28 days prior randomization); and
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be =< 5 x ULN (obtained within 28 days prior randomization)
  • Serum creatinine =< 1.5 x ULN for the lab or measured or calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior randomization)
  • A urine sample tested for proteinuria by the dipstick method must indicate 0 -1+ protein; if dipstick reading is >= 2+, a 24-hour urine specimen must demonstrate < 1.0 g of protein per 24 hours
  • International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =< 1.5 x ULN for the lab within 28 days before randomization; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history
  • Pregnancy test done within 14 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the last dose of mFOLFOX6; men with female partners of child-bearing potential must agree to use adequate contraception prior to the study, for the duration of study participation, and for 6 months after the last dose of bevacizumab and 6 months after the last dose of mFOLFOX6

Gender

N/A

Monetary compensation

No

Can be done from home

No

Keywords

colon cancer, metastatic cancer, liver metastases

Principal Investigator

Thomas J George, Jr, M.D.

Department

MD-HEMATOLOGY/ONCOLOGY

Contact Information

tgeorge@ufl.edu

352-273-8008


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