This phase II trial compares the usual treatment alone (carboplatin, pemetrexed, and bevacizumab) to using immunotherapy (atezolizumab) plus the usual treatment in treating patients with peritoneal mesothelioma. The usual treatment consists of surgery or chemotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill cancer cells. 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 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 atezolizumab with usual treatment may work better than usual treatment alone.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Given IV
Given IV
Undergo blood and tissue sample collection
Given IV
Undergo CT scan
Undergo surgery
Undergo HIPEC
Given IV
Undergo PET scan
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
SUSPENDEDUniversity of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
RECRUITINGCarle at The Riverfront
Danville, Illinois, United States
RECRUITINGCarle Physician Group-Effingham
Effingham, Illinois, United States
Response rate
Will be compared between arms.
Time frame: Up to 4 years after study activation
Major pathologic response rate
The proportion of patients with a pathologic response will be calculated and compared between arms and 95% confidence intervals reported. The chi-square test will be used to compare the rates between arms.
Time frame: Up to 3 years
Completeness of cytoreduction
Will be estimated.
Time frame: Up to 3 years
Conversion rate to surgical resection among those not deemed to be surgical candidates
Will estimate the conversion rate to surgical resection among those not deemed to be surgical candidates prior to treatment and provide the 95% confidence interval as well.
Time frame: Up to 3 years
Progression-free survival (PFS)
Will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
Time frame: From study entry to the first of either disease progression or death from any cause, where disease progression will be determined based on Response Evaluation Criteria in Solid Tumors 1.1 criteria, assessed up to 3 years
Overall survival
Will be estimated using the Kaplan-Meier method, where the log-rank test will be used to compare the 2 treatment arms.
Time frame: From study entry to death from any cause, assessed up to 3 years
Incidence of adverse events
The maximum grade for each type of adverse event will be summarized using Common Terminology Criteria for Adverse Events version 5.0. The frequency and percentage of grade 3+ adverse events will be compared between the 2 treatment arms. Comparisons between arms will be made by using either the Chi-square or Fisher's Exact test.
Time frame: Up to 3 years
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Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
RECRUITINGCarle Cancer Center
Urbana, Illinois, United States
RECRUITINGThe Carle Foundation Hospital
Urbana, Illinois, United States
RECRUITINGUniversity of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
ACTIVE_NOT_RECRUITINGAlliance for Clinical Trials in Oncology
Boston, Massachusetts, United States
RECRUITINGSanford Joe Lueken Cancer Center
Bemidji, Minnesota, United States
RECRUITING...and 29 more locations