Last updated on November 2019

Combination Chemotherapy Bevacizumab and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer


Brief description of study

This randomized 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 to other places in the body. Drugs used in chemotherapy, 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. Immunotherapy with monoclonal antibodies, such as bevacizumab and 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.

Detailed Study Description

PRIMARY OBJECTIVES:

I. To determine the efficacy, based on progression-free survival (PFS), of fluorouracil, oxaliplatin, and leucovorin calcium (mFOLFOX6)/bevacizumab plus atezolizumab (combination) and atezolizumab (single agent) as compared to mFOLFOX6/bevacizumab (control).

SECONDARY OBJECTIVES:

I. To compare the overall survival. II. To compare the objective response rates (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

III. To determine the safety profiles of the combination of mFOLFOX6/bevacizumab/atezolizumab and atezolizumab monotherapy in patients with mismatch-repair deficient (dMMR) metastatic colorectal cancer (mCRC).

IV. To compare the surgical conversion rate. V. To determine the duration of response and stable disease. VI. To determine the progression-free survival (PFS) by retrospective central independent scan review.

EXPLORATORY OBJECTIVES:

I. To compare the health-related quality of life and patient-reported symptoms.

TRANSLATIONAL OBJECTIVES:

I. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.

II. To compare disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Cycles of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Cycles of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.

Clinical Study Identifier: NCT02997228

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