Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma
Start Date
3/22/2022
Completion Date
8/20/2026
Summary
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.
Detailed Description
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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Atezolizumab
Bevacizumab
Biospecimen Collection
Carboplatin
Computed Tomography
Cytoreductive Surgery
Hyperthermic Intraperitoneal Chemotherapy
Pemetrexed
Positron Emission Tomography
Conditions
Locations
Mayo Clinic Hospital in Arizona
Phoenix, Arizona 85054
United States
Alliance for Clinical Trials in Oncology
Chicago, Illinois 60606
United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637
United States
Carle at The Riverfront
Danville, Illinois 61832
United States
Carle Physician Group-Effingham
Effingham, Illinois 62401
United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938
United States
Carle Cancer Center
Urbana, Illinois 61801
United States
The Carle Foundation Hospital
Urbana, Illinois 61801
United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536
United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Unity Hospital
Fridley, Minnesota 55432
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Mayo Clinic in Rochester
Rochester, Minnesota 55905
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Rice Memorial Hospital
Willmar, Minnesota 56201
United States
Sanford Cancer Center Worthington
Worthington, Minnesota 56187
United States
Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio 43210
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania 15232
United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota 57104
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
UT MD Anderson - The Woodlands
Conroe, Texas 77384
United States
UT MD Anderson Cancer Center
Houston, Texas 77030
United States
UT MD Anderson - West Houston
Houston, Texas 77079
United States
UT MD Anderson - League City
League City, Texas 77573
United States
UT MD Anderson - Sugar Land
Sugar Land, Texas 77478
United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin 54911
United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin 54701
United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin 54449
United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin 54548
United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin 54868
United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin 54482
United States
Marshfield Medical Center - Weston
Weston, Wisconsin 54476
United States