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

Jagiellonian University

Status and phase: Enrolling; Phase 3

Conditions: Gastric Cancer

Treatments: Combination Product: FLOT + HIPEC + Surgery; Combination Product: FLOT + Surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT04597294

Gastric CHIMERA Trial

2019/ABM/01/00020-00 (Other Grant/Funding Number)

2020-001419-25 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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600 participants in 2 patient groups

Perioperative FLOT + prophylactic HIPEC + surgery

Experimental group

Description:

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)

Treatment:

Combination Product: FLOT + HIPEC + Surgery

Perioperative FLOT + surgery

Active Comparator group

Description:

Standard treatment regimen for advanced gastric cancer

Treatment:

Combination Product: FLOT + Surgery