This phase I trial studies how well nivolumab and combination chemotherapy before surgery work in treating patients with pleural malignant mesothelioma that can be removed by surgery (resectable). Nivolumab is a type of medication called an antibody, which is like the proteins made by the immune system to protect the body from harm. Nivolumab blocks the protein PD 1 (programmed cell death receptor 1) that usually acts as a “brake” on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, 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. Giving nivolumab and combination chemotherapy may work better in treating patients with pleural malignant mesothelioma compared to combination chemotherapy alone.
Additional locations may be listed on ClinicalTrials.gov for NCT04162015.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To determine the feasibility of administering nivolumab in combination with pemetrexed and cisplatin or carboplatin for potentially resectable malignant pleural mesothelioma.
SECONDARY OBJECTIVES:
I. Evaluate the safety of nivolumab in combination with pemetrexed and cisplatin or carboplatin for potentially resectable malignant pleural mesothelioma.
II. Evaluate the post-operative safety of prior receipt of nivolumab in combination with pemetrexed and cisplatin or carboplatin.
III. Determine the response rate to preoperative treatment with nivolumab and pemetrexed with cisplatin or carboplatin.
EXPLORATORY OBJECTIVES:
I. Evaluate changes in immune cytokines and chemokines.
II. Evaluate T cell activation and exhaustion before and after systemic treatment.
III. Evaluate changes in the T cell repertoire.
IV. Evaluate changes in immune cytokines and chemokines, T-cell activation and exhaustion, and T-cell repertoire with treatment response.
V. Determine the rate and extent of pathologic response in resected specimens.
VI. Disease-free survival.
VII. Overall survival.
OUTLINE:
Patients receive nivolumab intravenously (IV) over 30 minutes, pemetrexed IV over 10 minutes, and cisplatin IV over 60 minutes (or carboplatin IV over 30 minutes instead of cisplatin) on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorMichael David Offin
