Prophylactic Preoperative HIPEC in Advanced Gastric Cancer at High Risk of Peritoneal Recurrence

Phase 3

Recruiting

• Conditions: Gastric Cancer
• Interventions: Combination Product: FLOT + Surgery; Combination Product: FLOT + HIPEC + Surgery

• Registration Number: NCT04597294
• Lead Sponsor: Jagiellonian University

Brief Summary

The study was designed to evaluate the efficacy of perioperative FLOT chemotherapy in combination with perioperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer at high risk of peritoneal metastases. The impact of treatment on peritoneal recurrence and survival over 6 months, 1, 3 and 5 years will be assessed.

Detailed Description

This is a randomized, multicenter, clinical trial in which 598 patients with advanced gastric cancer at high risk of peritoneal metastases are randomly allocated to receive either preoperative hyperthermic intraperitoneal chemotherapy (HIPEC) plus gastrectomy (experimental group) or gastrectomy alone (control group). All patients, regardless of allocation, will additionally receive 4 cycles of FLOT chemotherapy (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 and 5-fluorouracil 2600 mg/m2) before surgery ± HIPEC and 4 cycles of FLOT chemotherapy after gastrectomy. The main outcome is frequency of peritoneal recurrence by 6-months post-operative. Patients will be followed for 5 years and undergo additional evaluations at 6 months, 1 year, 3 and 5 years.

The study will take place at 7 hospitals across Poland. All participating centers have the equipment and skills to perform all necessary procedures in this study. The below centers specialize in the treatment of stomach cancer with many documented years of experience. They are trained in the maintenance of a register, possess the skills to conduct appropriate research analyses and are equipped with a system for assessing the quality of both surgical and oncological treatment.

Study Timeline

• Study First Submitted: 2020-10-15
• Study First Submitted QC: 2020-10-20
• Study First Posted: 2020-10-22
• Study Start: 2021-08-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-06
• Primary Completion: 2026-01
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Gastric cancer confirmed histopathologically in tumor specimens.
• Age 18-75 years.
• Advanced gastric cancer cT3 / cT4a / N0-3b.
• No distant metastases on computed tomography (CT) scan of the chest, abdomen and pelvis (cM0).
• Written consent to participate in the study.

Exclusion Criteria

• No clear histopathological confirmation of gastric cancer.
• Age > 75 years.
• Poor general condition (Performance Status 3 or more on the Eastern Cooperative Oncology Group (ECOG)/World Health Organization scale).
• Previous abdominal surgery (including oncological surgery), other than laparoscopic cholecystectomy or appendectomy (open or laparoscopic).
• Pregnancy and lactation.
• Refusal to participate or an inability to provide written consent.
• Coexisting cancer in another location.
• Systemic treatment or radiotherapy for another cancer.
• Dysphagia requiring surgical treatment (gastric resection or nutritional jejunostomy) before starting neoadjuvant treatment and indication for accelerated surgery for other reasons.
• Disqualification for perioperative FLOT4 chemotherapy as decided by a multi-specialist consultation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Perioperative FLOT + surgery	FLOT + Surgery	Standard treatment regimen for advanced gastric cancer
Perioperative FLOT + prophylactic HIPEC + surgery	FLOT + HIPEC + Surgery	After 4 doses of preoperative FLOT chemotherapy diagnostic laparoscopy will be performed - patients without distant metastases will be randomised, in those randomised to experimental arm HIPEC with irinotecan will be performed (a dose of 300 mg/m2 body surface area will be administered over 45 minutes at a temperature of 42 degrees Celsius)

Primary Outcome Measures

Name	Time	Method
Peritoneal recurrence rate	6 months	The rate of peritoneal recurrences at 6 month time from randomisation

Secondary Outcome Measures

Name	Time	Method
Systemic recurrence rate	5 years	Systemic recurrence rate at 5 year follow-up
Treatment-related quality of life assessed by Quality Of Life Questionnaire (QLQ) C30 version 3.0	6 months	Score range 0-100, higher score represents a higher (better) level of functioning
Local recurrence rate	5 years	Locoregional recurrence rate at 5 year follow-up
Complications rate	6 months	According to CTCAE version 5 and Clavien-Dindo classification
Overall survival	5 years	Overall survival at 5 year follow-up
Treatment-related quality of life assessed by Quality of Life Questionnaire-Stomach (STO22)	6 months	Score range 0-100, higher scores represent worse quality of life

Trial Locations

Locations (1)

Department of General, Oncological, Gastroenterological Surgery and Transplantology; 🇵🇱 Krakow, Lesser Poland Voivodship, Poland