FRONTiER: A feasibility trial of nivolumab with neoadjuvant CF or DCF therapy for locally advanced esophageal carcinoma

Abstract

Background: The standard neoadjuvant chemotherapy (NAC) in Japan for locally advanced esophageal squamous cell cancer (ESCC) is chemotherapy with CDDP + 5-FU (CF). Docetaxel (DTX) + CF (DCF) is considered a promising regimen, which has been evaluated in a phase III study, JCOG1109. Nivolumab (Nivo) has shown promising efficacy in unresectable ESCC. In a preclinical study immune-checkpoint inhibito (ICI) have shown efficacy as NAC and may work better than when used as adjuvants. Nivo monotherapy showed a major pathologic response in 43% of lung cancer patients (pts), but it was not shown whether ICI also work with chemotherapy that can lead to myelosuppression. The operative mortality and morbidity after use of ICI as NAC in ESCC are unknown. Trial design: This multi-cohort phase I study is designed to evaluate the safety and efficacy of ICI combined with NAC in ESCC. Histologically proven ESCC pts with cT1N1 3M0 or cT2-3N0-3M0 (8th-UICCTNM classification), 20-75 years old, PS 38 degree fever or grade 4 neutropenia lasting 3 days or longer, grade 4 thrombocytopenia lasting 3 days or longer, non-hematological toxicities of grade 3 or higher, grade 4 post-operative adverse events or grade 3 post-operative adverse events excluding hematological toxicity, anastomotic leak, pleural effusion and lung infection. 6 pts are planned to enroll to each cohort and less than one DLT was determined as safety among 6 pts. After this evaluation, we will add 12 pts as an expanded cohort.