This randomized clinical trial studies radiation therapy and MK-3475 in treating patients with head and neck cancer, kidney cancer, melanoma, or lung cancer that has returned, has spread to other parts of the body, or cannot be removed by surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as MK-3475, may block tumor growth by targeting certain cells and causing the immune system to attack the tumor. Studying the effects of MK-3475 with radiation therapy on the body may help doctors learn whether it may be an effective treatment for these solid tumors.
PRIMARY OBJECTIVES: I. To investigate the immunomodulatory activity of radiation therapy (RT) or RT in combination with anti-programmed cell death 1 (PD)-1 antibody (MK-3475) in patients with recurrent/metastatic head and neck cancer, renal cell cancer, melanoma and lung cancer. SECONDARY OBJECTIVES: I. To explore whether programmed cell death ligand 1 (PD-L1) expression is associated with treatment response to the combination of RT and PD-1 blockade in renal cell cancer (RCC), head and neck cancer (HNC), lung cancer and melanoma. II. To explore whether circulating tumor cells can be used to determine PD-L1 expression. III. To explore other immune-related biomarker changes after RT: soluble PD-L1, cytokines etc. OUTLINE: Patients are randomized to 1 of 4 treatment arms. ARM A1: Patients undergo radiation therapy on day 1 per standard of care and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 intravenously (IV) over 30 minutes on day 1. Courses of MK-3475 repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM A2: Patients undergo radiation therapy on days 1-5 and then undergo biopsy 3-10 days later. Beginning 0-7 days after biopsy, patients receive MK-3475 as in Arm A1. ARM B1: Patients receive one dose of MK-3475 IV over 30 minutes on day 1 and then undergo 1 fraction of RT. Patients then receive MK-3475 IV over 30 minutes in the absence of disease progression or unacceptable toxicity. ARM B2: Patients receive MK-3475 as in Arm B1 and undergo 5 fractions of RT. After completion of study treatment, patients are followed up at approximately 30 days and then every 8 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Undergo RT
Given IV
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Change in PD-LI levels
Within each cohort, the significance of change in PD-L1 will be assessed using an exact one-sided sign test. The null hypothesis is that the average change (post-pre) is less than or equal to 0 while the alternative hypothesis is that the average change is greater than 0. The proportion of patients with improvement will be estimated along with an exact 95% confidence interval. As an exploratory analysis, the proportion will also be estimated separately within each cohort for the head and neck cancer patients.
Time frame: Baseline to up to 10 days after last dose of RT
Response rate
Summarized by treatment cohort along with exact 95% binomial confidence intervals.
Time frame: Up to 4 years
Rate of toxicities
Summarized by treatment cohort along with exact 95% binomial confidence intervals.
Time frame: Up to 4 years
Progression-free survival
Estimated by treatment cohort using the Kaplan-Meier method.
Time frame: Up to 4 years
Biomarker levels
Repeated biomarker measurements will be modeled using mixed effects linear regression.
Time frame: Up to 10 days after last dose of RT
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