Phase II trial of systemic therapy plus intraperitoneal (IP) paclitaxel (PTX) in gastric/GEJ cancer peritoneal carcinomatosis (GPC): STOPGAP trial.

Abstract

359 Background: Peritoneal carcinomatosis (PC) is a common and deadly metastasis in gastric cancer. Systemic therapy alone may not adequately treat PC due to limited perfusion across peritoneum as result of blood-peritoneal barrier. Hence, combining intraperitoneal (IP) chemotherapy with systemic therapy is a viable alternate strategy to treat PC. We sought to evaluate the safety, feasibility, and preliminary efficacy of iterative normothermic IP PTX plus systemic therapy as consolidation strategy during first-line treatment. Methods: STOPGAP is a single center, single arm, open label phase II trial. Patients (pts) with histology proven gastric/GEJ (Siewert 3) adenocarcinoma with peritoneal involvement and no evidence of visceral metastasis who had no evidence of disease progression after 3-6 months of systemic treatment were eligible. After diagnostic laparoscopy (diag lap), and IP port placement, pts were treated with IP PTX 40 mg/m2 plus IV PTX 50 mg/m2, leucovorin 20 mg/m2 and 5-fluorouracil 400 mg/m2 (bolus) on days1 and 8, every 21 days for 4 cycles. If indicated, anti-PD1 antibody +/- trastuzumab were continued as before enrollment. Pts without progression after 4 cycles underwent repeat diag lap. Pts with peritoneal cancer index (PCI) ≤10 were considered for cytoreduction (CRS) with heated IP chemotherapy (HIPEC). IP PTX was discontinued after CRS. The primary endpoints were safety and feasibility and 12-months progression free survival (PFS12); secondary endpoints included overall survival (OS) and patient- reported outcomes (EuroQol-5D-5L). Results: Between May 2021 and July 2025, 31 pts were enrolled. Median age 50 years, M:F-15:16, median PCI=8 at enrollment (range 0-36); PCI 0 n=4,1-6 n=9, 7-14 n=10, ≥15 n=8. 98% of pts completed all 4 cycles of protocol treatment. G3 AEs occurred in 15 pts (48.3%). The most common AE was anemia (n=7; 21.9%). 11/31(35.4%) pts underwent CRS (CC-0:100%). In CRS cohort, median PCI at enrollment was 6 (0-24) and at CRS was 1 (0-10). No pts had anastomotic leaks or 30-day readmissions. The PFS12 was 28% (95% CI 13%:46%). The median PFS and OS are shown in table. Conclusions: Iterative normothermic IP PTX plus systemic treatment in GPC is safe and feasible, with encouraging clinical efficacy and safety in historically poor risk patients. The ongoing Phase 2/3 EA2234 STOPGAP II randomized trial will investigate the OS benefit of this approach compared to systemic therapy alone. Clinical trial information: 04762953 . Median PFS and OS from diagnosis and on study (months (95% CI). Median PFS from diagnosis Median PFS On study Median OS from diagnosis Median OS On study All patients (n=31) 11.5 (8.3-14.8) 5.1 (3.4-8.1) 17.5 (12.6-19.3) 11.1 (7.7-12.9) No CRS* (n=17) 8.3 (6.9-11.3) 3.4 (2.4-4.9) 13.9 (9.3-16.3) 7.7 (5.0-10.0) CRS** (n=11) 22.2 (11.9-NA ) 18.4 (7.9-NA ) 38 (17.5- NA ) 33.5 (11.7-NA ) *P<0.001 CRS vs. no CRS; **3 pts are awaiting CRS.