D2 Resection and HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) in Locally Advanced Gastric Carcinoma

Study Overview
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Brief Summary
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A prospective, opened, multicentric, randomised, phase III trial with two arms: Arm A: curative gastrectomy with D1-D2 lymph node dissection + HIPEC with oxaliplatin Arm B: curative gastrectomy with D1-D2 lymph node dissection Main objective: Compare overall 5-year survival rates in patients surgically treated for advanced gastric adenocarcinoma (T3, T4 and/or N+ and/or with positive peritoneal cytology), treated either with curative gastrectomy and adjuvant HIPEC, or with curative gastrectomy alone.

Official Title
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GASTRICHIP : D2 Resection and HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) in Locally Advanced Gastric Carcinoma. A Randomized and Multicentric Phase III Study.

Conditions
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Gastric Adenocarcinoma

Intervention / Treatment
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* Drug: HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) with oxaliplatin
* Procedure: Curative gastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 < age ≤ 75 years old White blood cells > 3,500/mm3, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3 Good renal functions, serum creatinine values being < 1.5 mg/dl and creatinine clearance > 60 ml/min Performance Status ≤1, Karnofsky Index ≥ 70% Serum bilirubin ≤ 2 mg/dl Having given written informed consent prior to any procedure related to the study. Covered by a Health System where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research Not under any administrative or legal supervision Histologically evidenced resectable T3 or T4 gastric adenocarcinoma for which a curative gastrectomy is scheduled, with invasion into the serosa AND/OR lymph node metastasis (determined from data obtained by endoscopic ultrasound and chest, abdomen and pelvis CT scan) AND/OR positive peritoneal cytology (sampled during the preoperative laparoscopy). AND/OR Perforated gastric adenocarcinoma AND/OR Siewert III adenocarcinoma of the cardia for which a gastrectomy by exclusive abdominal laparotomy is scheduled Females of childbearing age potential and male subjects with partners of childbearing potential using efficient contraceptive measures (as judged by the investigator).Subjects randomised in the arm with HIPEC should be informed and accept that these requirements should also extend to : 4 months after the treatment with Oxaliplatin for female subjects, 6 months after the treatment with Oxaliplatin for male subjects. Exclusion Criteria: Prior malignant tumors with detectable signs of recurrence Gastric stump adenocarcinoma Presence of comorbidities, notably serious chronic diseases or organ failure General conditions Any subject in exclusion period of a previous study according to applicable regulations Pregnancy or breastfeeding Females of childbearing age potential or male subjects with partners of childbearing potential not using medically accepted contraceptive measures, as judged by the investigator Interfering substance Contraindication to any drug contained in the chemotherapy regimen Specific to the study Life threatening toxicity before surgery Distant metastases (liver, lung. ovaries, etc) Tumoral infiltration of the head or body of the pancreas Patients presenting an adenocarcinoma of the cardia Siewert I or II Existence of macroscopic peritoneal implants Patients with clinically significant ascites (> 500 cc) even if cytology is negative for cancer cells, in the absence of other non-malignant causes of ascites

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curative Gastrectomy + HIPEC<br>Curative gastrectomy with D1-D2 lymph node dissection + HIPEC with oxaliplatin | Drug: HIPEC (Hyperthermic Intraperitoneal Chemoperfusion) with oxaliplatin<br>* After the D2 resection is complete HIPEC can start. A roller pump forces the chemotherapy solution (oxaliplatin 250 mg/m² with 2 Liters of G5%/m²) into the abdomen through the inflow catheter and pulls it out through the drains. A heat exchanger keeps the intraperitoneal fluid at 42°-43°C.<br>Procedure: Curative gastrectomy<br>* All the patients will undergo a D1-D2 gastrectomy carried out according to Japanese guidelines and to the European recommendations for the preservation of spleen and pancreas<br>|
| Other: Curative Gastrectomy<br>Curative gastrectomy with D1-D2 lymph node dissection | Procedure: Curative gastrectomy<br>* All the patients will undergo a D1-D2 gastrectomy carried out according to Japanese guidelines and to the European recommendations for the preservation of spleen and pancreas<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the date of surgery to the date of death or to the end of follow-up | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival | From the date of surgery to the date of recurrence or to the end of follow-up | 5 years | 
| Recurrence-free survival | From the date of surgery to the date of recurrence or to the end of follow-up | 3 years | 
| Locoregional-free survival | From the date of surgery to the date of locoregional recurrence or to the end of follow-up | 5 years | 
| Treatment-related morbidity | Common Terminology Criteria for Adverse Events v4.0 | During the 60th postoperative days | 
| Treatment-related mortality |  | During the 60th postoperative days | 
| Score QLQ-C30 | Quality of life is assessed with EORTC questionnaire QLQ-C30 | 3 months (M3), 6 months (M6) and 12 months (M12) after surgery +/- HIPEC procedure. | 
| Score QLQ-STO 22 | Quality of life is assessed with EORTC questionnaire QLQ-STO 22 | 3 months (M3), 6 months (M6) and 12 months (M12) after surgery +/- HIPEC procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric adenocarcinoma, HIPEC, Oxaliplatin, Signet ring cell