Phase II/III randomized trial of exclusive chemoradiotherapy with or without dose escalation in locally advanced esophageal carcinoma: The CONCORDE study (PRODIGE 26).

Abstract

TPS190 Background: INT 0123 failed to demonstrate an overall survival benefit with chemoradiotherapy dose escalation in locally advanced esophageal cancer. Nearly 45% of the patients had local persistent or recurrent disease. Several drawbacks surround the interpretation of the results of INT 0123. Improvements in target definitions with planning CT and 18F FDG PET/CT in keeping with improvements in radiation dose delivery that better protect healthy tissues with 3D conformal radiation therapy and/or IMRT should lead to the retesting of dose escalation in the modern era of new technologies. Methods: Patients are randomized into two groups: Experimental group: 40Gy ENI followed by a 26-Gy boost to the primary tumor and involved nodes (i.e. 33 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Control group: 40Gy ENI followed by a 10-Gy boost to the primary tumor and involved nodes (in 25 daily fractions of 2Gy) with concomitant and adjuvant FOLFOX-4 weeks 1, 3, 5, 7, 9 and 11. Randomization using minimization to ensure balanced allocation across: Center / Adeno vs Squamous cell carcinoma / stage III vs I-II / weight loss / 3D-CRT vs IMRT. The principal hypothesis is that the rate of survival without locoregional relapse at 2 years will reach 50% in the reference arm and 65% in the experimental arm (Hazard ratio = 0.62). With a risk α = 0.05 (bilateral test) and β = 0.15 (power 85%). If we use a rate of 5% for lost to follow-up, it will be necessary to recruit 266 patients. The main inclusion criteria are: age < 75 years, WHO Status 0, 1 and 2, Enteral or parenteral feeding planned before the start of treatment if oral calorie intake < 1500 kcal, Histologically proven carcinoma of the esophagus, adenocarcinoma or squamous cell, T3, N0-N3, M0 (UICC 7thedition), T1-T2, N0-N3, M0 with a contra-indication for surgery, Absence of tracheo-esophageal fistula, Absence of thoracic or upper abdominal irradiation for another tumor, Written informed consent. 141 of the 160 patients required in phase II of the trial were included by September 22nd 2015. (ClinicalTrials.gov Identifier: NCT01348217). Clinical trial information: NCT01348217.