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

A Randomized, Multicenter Clinical Trial Comparing the Combination of Perioperative FLOT Chemotherapy and Preoperative Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Plus Gastrectomy to Perioperative FLOT Chemotherapy and Gastrectomy Alone in Patients With Advanced Gastric Cancer at High Risk of Peritoneal Recurrence

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Combination product: FLOT + HIPEC + Surgery; Combination product: FLOT + Surgery

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 Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Piotr Richter, Professor; Phone Number: +48124002400; Email: piotr.richter@uj.edu.pl

Study Locations

• Poland
  • Lesser Poland Voivodship
    • Krakow, Lesser Poland Voivodship, Poland, 30-688
      • Recruiting
      • Department of General, Oncological, Gastroenterological Surgery and Transplantology
      • Contact: Piotr Richter, Professor; Phone Number: +48124002400; Email: piotr.richter@uj.edu.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Perioperative FLOT + prophylactic 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)	Combination product: FLOT + HIPEC + Surgery; HIPEC with irinotecan after 4 doses of preoperative FLOT chemotherapy; Other Names: Prophylactic HIPEC
Active Comparator: Perioperative FLOT + surgery; Standard treatment regimen for advanced gastric cancer	Combination product: FLOT + Surgery; Perioperative FLOT chemotherapy (4 doses before and 4 doses after gastrectomy) and surgery; Other Names: Perioperative FLOT + Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal recurrence rate	The rate of peritoneal recurrences at 6 month time from randomisation	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival at 6 month follow-up	6 months
Overall survival	Overall survival at 3 year follow-up	3 years
Overall survival	Overall survival at 5 year follow-up	5 years
Local recurrence rate	Locoregional recurrence rate at 3 year follow-up	3 years
Systemic recurrence rate	Systemic recurrence rate at 3 year follow-up	3 years
Local recurrence rate	Locoregional recurrence rate at 5 year follow-up	5 years
Systemic recurrence rate	Systemic recurrence rate at 5 year follow-up	5 years
Complications rate	According to CTCAE version 5 and Clavien-Dindo classification	6 months
Treatment-related quality of life assessed by Quality Of Life Questionnaire (QLQ) C30 version 3.0	Score range 0-100, higher score represents a higher (better) level of functioning	6 months
Treatment-related quality of life assessed by Quality of Life Questionnaire-Stomach (STO22)	Score range 0-100, higher scores represent worse quality of life	6 months

Collaborators and Investigators

• Sponsor: Jagiellonian University
• Investigators: Study Director: Piotr Richter, Professor, Jagiellonian University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; FLOT; HIPEC; Lymphadenectomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Recurrence
• Other Study ID Numbers: Gastric CHIMERA Trial; 2020-001419-25 (EudraCT Number); 2019/ABM/01/00020-00 (Other Grant/Funding Number: Medical Research Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No