نبذة مختصرة : BACKGROUND: The immunogenic cell death induced by radiotherapy (RT) has been demonstrated to enhance the systemic antitumor effect of immune checkpoint inhibitors (ICIs). The incorporation of RT into ICIs has the potential to mitigate the occurrence of early treatment failure, particularly with dual ICI combination, in patients with advanced or recurrent esophageal cancer. METHODS: This randomized phase II trial, initiated in November 2024, aims to explore the superiority of the combination of RT with nivolumab plus ipilimumab over nivolumab plus ipilimumab alone in patients with advanced or recurrent esophageal squamous cell carcinoma. The primary endpoint is progression-free survival, while the secondary endpoints include overall survival, response rate, duration of response, and adverse events. We assumed a 6-month PFS of 35% in the nivolumab plus ipilimumab alone arm and expected a 15% increase in the 6-month PFS for the RT with nivolumab plus ipilimumab arm (HR, 0.66). The total required sample size was calculated to be 70 (35 per arm) to achieve a desired power of 80% with an overall one-sided alpha of 20%, an accrual period of 2.5 years, and a follow-up period of 1 year. A total of 74 patients will be enrolled from 41 institutions in Japan. An ancillary study analyzes cytokine profiles and phenotypic characteristics in peripheral blood mononuclear cells during treatment with the protocol. DISCUSSION: The objective of this trial is to assess the safety and efficacy of RT in combination with dual ICIs in reducing early treatment failure and improving outcomes with translational research. Findings from this trial will inform a future phase III trial in this patient population. TRIAL REGISTRATION: This trial has been registered on November 5th, 2024, in the Japan Registry of Clinical Trials as jRCT1031240461 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT1031240461).
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