7H-14-1 An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Head and neck carcinomas (HNC) describe cancers of the upper digestive tract which include squamous cell cancers (SCCHN) of the mouth, throat, and vocal chords. At present, there is no effective standard of care that provides survival benefits beyond 4 - 6 months in second line treatment of SCCHN that spreads or returns and does not respond to platinum treatment (refractory). Nivolumab is a drug that binds to a tumor cell receptor that blocks the immune system, thus allowing the immune system to attack tumor cells. Nivolumab has demonstrated clinical activity across several tumor types, but there has been no clinical trial so far to study the clinical benefit of nivolumab in SCCHN. Cetuximab, methotrexate, and docetaxel, which appear to be the most active in the platinum refractory setting, have approved indications as single agents for treating SCCHN and will be used as the Investigator's Choice in this study. The objective of this study is to compare progression free survival (PFS) and overall survival (OS) of Nivolumab to Investigators Choice in subjects who have tumor progression within 6 months of last dose of platinum therapy.
Patients who will be enrolled for this study will have laboratory confirmed SCCHN whose disease has spread or returned within 6 months of being treated with a platinum based therapy. Participants will be randomized to receive one of the following: nivolumab, cetuximab, methotrexate, or docetaxel. During the study, participants in all groups will have the study procedures done during each cycle as stated in the protocol. All participants will stop taking study drug(s) if their disease worsens, they have another illness which prevents them from taking the study drug(s), they cannot tolerate the side effects, they withdraw from the study, their study doctor thinks that being on the study is no longer in their best interest, or the sponsor stops the study. All participants will be followed for 35 days and 80 days after stopping the study drug(s), and then every 3 months until death.
Subject characteristics including demographics, baseline performance status, disease
characteristics and baseline laboratory parameters will be summarized by randomized treatment
arm, as well as pooled across randomized treatment arm. A two-sided 0.03 log-rank test will be used to do a formal comparison of PFS across all treatment arms. Median PFS will be estimated via the Kaplan-Meier product limit method. Two-sided 95% confidence intervals (CI) for the median PFS will be computed for each randomized arm. Kaplan-Meier plots of PFS will be presented. Hazard ratios (HR) and corresponding two-sided (1-adjusted )% CI will be estimated using a Cox proportional hazards model, with treatment arm as a single covariate, stratified by the above factor, corresponding to each comparison of PFS. OS will be compared between the treatment arms among all randomized subjects using a two sided, = 0.02 level log-rank test (adjusted for interim analysis), stratified using the same factor as in PFS.