A multicenter, open-label, randomized phase II study evaluating adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (CAPE-RT) in patients with operated gallbladder adenocarcinoma (GBC): The GECCOR-GB trial

4017 Background: Adjuvant gemcitabine plus cisplatin (GC) and concurrent chemo-radiotherapy are commonly used treatment options for resected GBC. Methods: GB-GECCOR is a multicentre, open-label randomized non-comparative phase II study in patients of Gallbladder cancer (GBC), with R0 or R1 resection within 3 months of randomization. Patients were randomized 1:1 to GC arm (Gem 1000 mg/m2 and Cisplatin 25mg/m2 on day 1 and 8, q 3 weeks) for 6 cycles or CAPE-RT arm {Capecitabine 1000mg/m2 BD on days 1-14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825mg/m2 twice) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary end point was 1-year disease-free survival (DFS). With 80% power to detect the difference between a 59% (minimum sufficient activity of the regimen) and a 77% (sufficient activity for future larger studies with the regimen) 1-year DFS rate assuming an attrition of 10%, a total of 90 patients were required for the study. Results: Between May 2019 and February 2022, 90 patients (45 in each arm), were included. Stage II and stage III GBC were seen in 50 (56%) and 40 patients (44%) respectively, with R0 resection observed in 86 patients (96%). Patient characteristics were well balanced between the 2 arms except for R1 resections which were greater in the CAPE-RT arm (p=0.041). With a median follow-up duration of 23 months, the 1-year DFS rate was 88.9% (95% CI: 79.5-98.3) in the GC group and 77.8% (95% CI: 65.4 – 90.2) in the CAPE-RT group, respectively. The most common AEs were grade 3/4 neutropenia in 6 patients (13.3%) in the GC group and grade 2/3 HFS in 14 patients (31.1.%) in the CAPE-RT group. The distant metastases were seen in 12 patients (26.6 %) in each arm and loco-regional metastases in 3 patients (6.6 %) in the GC arm. Conclusions: In this study of operated GBC, GC and CAPE-RT successfully achieved the minimum pre-specified DFS rates. Within the confines of a non-comparative randomised study, GC had narrowed the gap in survivals of stage III vs. stage II GBCs, which was not noted in the CAPE-RT arm. This study results give credence to the use of both regimens as reasonable standards of care till evaluation in larger phase 3 studies. Clinical trial information: CTRI/2019/05/019323 . [Table: see text]