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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Combination Product: FLOT + HIPEC + Surgery
* Combination Product: FLOT + Surgery


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization 1:1
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FLOT, Gastric cancer, Lymphadenectomy, HIPEC