Colorectal Cancer Metastatic dMMR/MSI-H Immuno-Therapy (COMMIT) Study: A Randomized Phase III Study of mFOLFOX6/Bevacizumab/Atezolizumab Combination Versus Single Agent Atezolizumab in the First-Line Treatment of Patients With Deficient DNA Mismatch Repair (dMMR)/Microsatellite Instability-High (MSI-H) Metastatic Colorectal Cancer

Plain English Summary

Testing the Addition of Atezolizumab to Combination Chemotherapy or Atezolizumab Alone for Metastatic Colon or Rectal Cancer, the COMMIT Study is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Metastatic Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v7. This trial tests a new combination of chemotherapy, bevacizumab, and atezolizumab for treating metastatic colorectal cancer. It's for patients with metastatic colorectal cancer who haven't had chemotherapy before. Participants will receive IV treatments and have blood and imaging tests. There are other treatments available, such as chemotherapy alone. The trial aims to enroll 120 participants.

Official Summary

This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of the tumor. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. You must be 18 years or older and have a diagnosis of metastatic colorectal cancer. You can't have had chemotherapy before, but you can have had one cycle of FOLFOX or CAPOX. You must have a mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) status. You must be in good health with no other serious illnesses. This trial is studying Metastatic Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v7, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how long patients can live without their cancer getting worse. The specific primary outcome measures are: Progression free survival (PFS) (From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial is important because it aims to improve survival rates and quality of life for patients with metastatic colorectal cancer. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Metastatic Colorectal Adenocarcinoma, Stage IV Colorectal Cancer AJCC v7, where improved treatment options are needed.

Investor Insight

The market for colorectal cancer treatments is large, with many competitors, but this trial could lead to a new effective treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have a mismatch repair deficiency or microsatellite instability-high status. You will receive IV treatments and have blood and imaging tests. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 120 participants

Interventions

• DRUG: Atezolizumab — Given IV
• BIOLOGICAL: Bevacizumab — Given IV
• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• PROCEDURE: Computed Tomography — Undergo CT or CT/PET
• DRUG: Fluorouracil — Given IV

Primary Outcomes

• Progression free survival (PFS) (From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years)

Secondary Outcomes

• Overall survival (OS) (The time from randomization to death from any cause, assessed up to 5 years)
• Objective response rate (ORR) (complete response [CR] or partial response [PR]) (Up to 5 years)
• Incidence of adverse events (Up to 30 days after last cycle)
• Rate of PFS (At 12 months)
• Disease control rate (CR + PR + stable disease [SD]) (At 12 months)

Full Eligibility Criteria

Inclusion Criteria:

* The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
* Age \>= 18 years
* 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 except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial
* 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; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible
* Documentation by PET/CT scan, CT scan, or MRI that the patient has 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 =\< 4 x ULN (upper limit of normal) (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)
* Calculated creatinine clearance \>= 30 mL/min (obtained within 28 days prior randomization)
* A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA), or a urine protein creatinine (UPC) ratio:

  * The dipstick method must indicate 0-1+ protein; if dipstick reading is \>= 2+, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
  * A urine protein creatinine (UPC) ratio must be \< 1.0; if the UPC ratio is \>= 1.0 a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours
  * Urinalysis must indicate \< 30 mg/dl. If urinalysis \>= 30 mg/dl, a 24-hour urine must be done and it must demonstrate \< 1.0 g of protein per 24 hours or a UPC ratio \< 1.0
* 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, regardless of PT/INR results
* Pregnancy test done within 28 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; administration of atezolizumab or mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; 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 and men must agree to use adequate contraception methods that result in a failure rate of \< 1% per year during the treatment period (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; a woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (\>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of \< 1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdr

Trial Locations

• Kingman Regional Medical Center, Kingman, Arizona, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• Kaiser Permanente-Anaheim, Anaheim, California, United States
• Kaiser Permanente-Baldwin Park, Baldwin Park, California, United States
• Kaiser Permanente-Bellflower, Bellflower, California, United States
• Alta Bates Summit Medical Center-Herrick Campus, Berkeley, California, United States
• John Muir Medical Center-Concord, Concord, California, United States
• Kaiser Permanente-Fontana, Fontana, California, United States
• Kaiser Permanente South Bay, Harbor City, California, United States
• Kaiser Permanente-Irvine, Irvine, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Colorectal cancer, metastatic colorectal adenocarcinoma, stage IV colorectal cancer, colorectal cancer, dMMR, MSI-H

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