NCT05001880

Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma

Phase 2 Randomized Trial of Neoadjuvant or Palliative Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Peritoneal Malignant Mesothelioma

Interventions

Type	Name	Description
BIOLOGICAL	Atezolizumab	Given IV
BIOLOGICAL	Bevacizumab	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood and tissue sample collection
DRUG	Carboplatin	Given IV
PROCEDURE	Computed Tomography	Undergo CT scan
PROCEDURE	Cytoreductive Surgery	Undergo surgery
DRUG	Hyperthermic Intraperitoneal Chemotherapy	Undergo HIPEC
DRUG	Pemetrexed	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET scan

Timeline

• Start date: 2022-03-22
• Primary completion: 2026-08-20
• Completion: 2026-08-20
• First posted: 2021-08-12
• Last updated: 2026-04-15

Locations

40 sites across 1 country: United States

Regulatory

• FDA-regulated drug study