Summary
STUDY IS CLOSED at Site - 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.
Description
PRIMARY OBJECTIVE:
I. To determine the efficacy, based on progression-free survival (PFS), of fluorouracil, oxaliplatin, and leucovorin calcium (modified [m]FOLFOX6)/bevacizumab plus atezolizumab (combination) as compared to single agent atezolizumab.
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 single agent atezolizumab and the combination of mFOLFOX6/bevacizumab/atezolizumab in patients with mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC).
IV. To determine the duration of response. V. To determine the duration of stable disease. VI. To determine the rate of progression-free survival (PFS) at 12 months. VII. To evaluate the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months.
TRANSLATIONAL OBJECTIVE:
I. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM I (CLOSED TO ACCRUAL 6/4/2020): 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. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with or without positron emission tomography (PET) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
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. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
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. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial.
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.