Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma

PRIMARY OBJECTIVE: I. To determine whether frontline treatment with carboplatin, pemetrexed, bevacizumab and atezolizumab results in a superior best response rate than carboplatin, pemetrexed and bevacizumab in patients with peritoneal mesothelioma as determined by Response Evaluation Criteria in Solid Tumors (RECIST). SECONDARY OBJECTIVES: I. To determine the safety, major pathologic response rates, and completeness of cytoreduction of patients treated with neoadjuvant carboplatin, pemetrexed, bevacizumab and atezolizumab or carboplatin, pemetrexed and bevacizumab. II. To determine the safety of patients treated with palliative carboplatin, pemetrexed, bevacizumab and atezolizumab or carboplatin, pemetrexed and bevacizumab. III. To determine whether frontline treatment with carboplatin, pemetrexed, bevacizumab and atezolizumab results in a superior metabolic response rate than carboplatin, pemetrexed and bevacizumab as determined by Positron Emission Tomography (PET) Response Criteria in Solid Tumors. IV. Explore the value that analysis of secondary computed tomography (CT) findings and quantitative fludeoxyglucose F-18 (FDG)-PET imaging adds to prognostic information and response assessment in this disease. V. Determine the number of patients who were deemed to have unresectable disease who are able to undergo surgery following treatment with carboplatin, pemetrexed, bevacizumab and atezolizumab or carboplatin, pemetrexed and bevacizumab due to dramatic response. VI. To compare the progression-free survival and overall survival between arms. VII. Results of the primary analysis will be examined for consistency, while taking into account the stratification factors and/or covariates of baseline quality of life (QOL) and fatigue. EXPLORATORY OBJECTIVE: I. To determine whether blood-based biomarkers including our recently described cell-free chromosomal junctions, soluble mesothelin-related peptides and megakaryocyte potentiating factor correlate with clinical outcomes data (i.e. overall survival \[OS\], progression-free survival \[PFS\], recurrence, response, etc.). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes, bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients not eligible for surgery may receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1 of each maintenance therapy cycle. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive bevacizumab IV over 30-90 minutes, carboplatin IV over 30 minutes, and pemetrexed IV over 10 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks, patients then undergo cytoreductive surgery and HIPEC. Patients not eligible for surgery may receive bevacizumab IV over 30-90 minutes with or without atezolizumab IV over 30-60 minutes on day 1 of each maintenance therapy cycle at the discretion of the investigator. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT scan, PET scan, and collection of blood and tissue samples throughout the study. After completion of study treatment, patients are followed up every 6 months for up to 3 years.