This phase I trial studies the side effects and how well nivolumab works when given together with radiation therapy or ipilimumab as adjuvant therapy in treating patients with Merkel cell cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons or other sources to kill tumor cells and shrink tumors. Giving nivolumab with radiation therapy or ipilimumab after surgery may kill any remaining tumor cells.
PRIMARY OBJECTIVES: I. To assess the tolerability of two different experimental immunotherapy regimens in the adjuvant setting in patients with Merkel cell carcinoma (MCC). SECONDARY OBJECTIVES: I. To assess the safety and tolerability profile of each of the treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. II. To assess the efficacy of each of the treatment arms according to recurrence-free survival (RFS) at one and half years, defined as the time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), whichever occurs first. III. To assess the efficacy of each of the treatment arms according to overall survival (OS) at three years, defined from the time of randomization and the date of death, compared to historical registry control. EXPLORATORY OBJECTIVES: I. To explore potential biomarkers, next generation T cell receptor (TCR) sequencing will be performed to identify and longitudinally track individual T cell clones thus granting a comprehensive insight into immunological changes that occur within the tumor and peripheral blood throughout the course of the disease. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Given IV
Given IV
Receive radiation therapy
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Percentage of patients completing 12 months of treatment
Will be estimated along with the 95% confidence interval for each arm based on the binomial distribution.
Time frame: Up to 12 months
Recurrence-free survival (RFS) one and half years
Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and overall survival (OS), for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.
Time frame: Time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), assessed up to one and half years.
Overall survival at three years
Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and OS, for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.
Time frame: Time from randomization to the date of death, assessed up to 3 years
Incidence of adverse events (AEs)
Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Side effects will be summarized by each treatment group.
Time frame: Up to 3 years post treatment
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