Protocol for a phase III randomized trial of chemoradiation and systemic chemotherapy vs. systemic chemotherapy alone in patients with unresectable nonmetastatic cholangiocarcinoma

Abstract

Background: Systemic doublet chemotherapy constitutes the current standard of care for patients with unresectable non-metastatic cholangiocarcinoma. The use of doublet chemotherapy is associated with median survival of 11.7 months. Concurrent chemo-radiation in this cohort is associated with similar overall survival however the impact of combination of chemoradiation and systemic chemotherapy on overall survival has not been investigated. The present phase III randomized study investigates the impact of chemoradiation in addition to systemic chemotherapy on overall survival.Methods: Patients older than 18 years of age with diagnosis of unresectable non-metastatic cholangiocarcinoma with performance status 0-2and preserved liver function (Child Pugh score up to B7) will be eligible for study participation. The trial is designed such that patients will undergo stratified randomization (extra-hepatic vs. intrahepatic) either into systemic chemotherapy (standard arm) or chemo-radiation and systemic chemotherapy arm (experimental arm). The primary aim of the study is to compare difference in overall survival. The secondary aims of the study will focus on loco regional progression free survival and cause specific survival. The study will also report on the acute and late toxicity, quality of life and resectability rates in both the study arms. To demonstrate 7-month improvement in overall survival from 11 to 18 months a sample size of 142 is needed. Accounting for attrition a total of 155 patients will be accrued. All study subjects will be accrued after written informed consent. The trial is approved by the institutional ethics review board.This trial is registered with ClinicalTrials.gov as NCT02773485