A randomized phase II/III trial of intraperitoneal paclitaxel plus systemic treatment vs systemic treatment alone in gastric carcinomatosis: STOPGAP II—ECOG-ACRIN EA2234.

TPS4241 Background: Thirty to forty percent of patients with gastric cancer will develop peritoneal carcinomatosis (PC), the survival of which remains poor despite systemic therapy (ST). Limited drug delivery into PC due to blood-peritoneal barrier is considered to decrease the effectiveness of ST. Hence, there is a critical need to develop novel treatment strategies to improve patient outcomes. Intraperitoneal (IP) paclitaxel (PTX) combined with ST had been studied extensively in Asia. In the US, STOPGAP I, a single institution phase II trial has established the safety and feasibility of IP PTX plus ST in Western patients with gastric PC. Based on these results, we developed STOPGAP II trial, which is designed to evaluate the survival benefits of IP PTX plus ST compared to ST alone in patients with gastric PC. Methods: ECOG-ACRIN EA 2234 STOPGAP II is a multi-center randomized phase II/III trial (NCT07001748) evaluating IP PTX plus ST compared to ST alone in patients with gastric PC. Eligible patients must have microsatellite stable gastric/gastroesophageal cancer (Siewert 3) with cytology positive disease or carcinomatosis detected by diagnostic laparoscopy (DL), laparotomy, or radiology and have undergone 3-6 months of first line ST. Patients must not have visceral metastases except ovarian metastases or clinically significant progression of PC. All enrolled patients will undergo DL with peritoneal cancer index (PCI) assessment within four weeks of registration. Patients will be randomized intraoperatively in 1:1 fashion to Arm A- ST or Arm B- IP PTX with ST. In patients randomized to Arm B, an IP port will be placed at the initial DL . Patients in Arm A will continue first line ST and patients in Arm B will receive 40 mg/m2 of IP PTX on days 1 and 8 combined with 50mg/m2 of IV PTX, 5 fluorouracil 400 mg/m2, leucovorin 20mg/m2. Immune checkpoint inhibitors and targeted agents will be continued as per standard of care. Patients will be stratified by PCI (0, 1-6, 7-14, versus >15) and first line ST type (chemo + targeted agent or immunotherapy versus chemotherapy alone). In both treatment arms, patients will undergo reevaluation with repeat imaging and if indicated, DL after three months. Patients with stable disease or response will continue the assigned treatment or could be considered for cytoreduction if PCI <7. The primary endpoints are progression free survival (phase II) and overall survival (OS) (phase III). Assuming the median OS of IP PTX and that of ST to be 22.5 and 12.5 months respectively, and accounting for attrition, 148 patients will be enrolled to achieve 90% power with a hazard ratio of 0.56 (one-sided type I error of 5%). The study is actively enrolling patients with results expected in 2031. Clinical trial information: NCT07001748 .