PRODIGE 51 - GASTFOX: Phase III randomised trial evaluating FOLFOX with or without DOCETAXEL (TFOX) as 1st line chemotherapy for locally advanced or metastatic oesophago-gastric adenocarcinoma

Abstract

Background: In advanced gastric cancer, doublet regimen with cisplatin and fluoropyrimidine is considered as a 1st‐line standard treatment (trt). Taxane is also effective in 2nd line. The addition of docetaxel (75 mg/m2) to cisplatin (75 mg/m2) and 5‐fluorouracil (“DCF regimen”) every 3 weeks has been shown to improve efficacy of 1st‐line trt in a phase III trial. However, this regimen was associated with more frequent grade 3‐4 toxicities, such as diarrhea, neutropenia and complicated neutropenia (febrile neutropenia or neutropenic infection). Oxaliplatin has been shown to be more tolerable than cisplatin with the same efficacy. The addition of docetaxel at 50 mg/m2 every 2 weeks to the FOLFOX (TFOX regimen) showed to be active and tolerable in phase II studies and less toxic as compared DCF regimen. The aim of this current phase III study is to compare FOLFOX to TFOX in 1st line trt of advanced gastric cancer. Trial design: The major eligibility criteria are: Patient ≥ 18 years,WHOPS ≤1, with histological proven gastric or gastro‐oesophageal junction HER2 negative adenocarcinoma, metastatic or locally advanced measurable disease (RECIST v1.1 criteria). Trt is administered every 14 days. Trt has to be administrated until disease progression or unacceptable toxicity. The primary criterion is radiological/clinical progression‐free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (5.5 months in FOLFOX arm vs 7.5 months in TFOX arm), HR=0.73. (α=5%, power of 90%, O'Brien ‐ Fleming function). An interim analysis is planned at 227 events (progression or death) for early efficacy or futility search. Secondary criteria are: overall survival, objective response rate, therapeutic index, toxicity, time to final deterioration in quality of life. Stratification factors are: centre,WHOPS, adjuvant chemotherapy or radio‐chemotherapy, tumour stage, primary tumour location and pathological subtype. 17 patients have been randomized over the 506 planned since 19/12/2016. (Table presented).