Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Gastric Carcinoma.GOETH Study

Study Overview
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Brief Summary
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This is a phase III randomized, multicenter study with two different arm: experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility in both arms. Patient will be randomized in a 1:1 ratio. Randomization will be performed during surgery if the total resection of tumor will be reached according to center and neoadjuvant chemotherapy as stratification variables.

Detailed Description
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This is a phase III randomized, multicenter study with two different arm: experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility. Patient will be randomized in a 1:1 ratio. Randomization will be performed during surgery if the total resection of tumor will be reached according to center and neoadjuvant chemotherapy as stratification variables. The primary objective of the study is to compare the efficacy of prophylactic surgery (radical gastric resection, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 versus standard surgery in terms of disease free survival (DFS). Patients affected by gastric carcinoma at high risk of developing peritoneal carcinomatosis will be randomized in this study.

Official Title
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Prophylactic Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC CO2) Versus Standard Surgery in Gastric Carcinoma at High Risk of Developing Peritoneal Carcinomatosis. Short and Long-term Outcomes Evaluation.A Collaborative Randomized Controlled Trial of: ACOI, FONDAZIONE AIOM, SIC, SICE, SICO. GOETH STUDY

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Procedure: Surgery plus HIPEC CO2
* Procedure: Standard surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically documented gastric carcinoma (diffuse/intestinal histotype) eligibile for R0. Presurgical or intraoperative stage T3-T4 N0-N+ primary tumour (TNM 8 th). Urgent presentation: perforation without purulent generalized peritonitis Positive cytology of peritoneal fluid (if previously obtained) Age ≥ 18 years and ≤75 years. Written informed consent. Exclusion Criteria: Gastroesophageal Junction (GEJ) cancer Distant metastatic disease (even if limited and completely resected) Peritoneal carcinomatosis History of tumor diagnosed in the 3 years before entering the study, except for topical and healed pathologies that do not need further treatment (e.g. non-melanoma skin carcinomas, superficial bladder carcinomas or in situ carcinoma of the breast or cervix). Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol. Poor general conditions (ECOG > 2). Impaired cardiac function (history of congestive heart failure or FE <40%). Clinically significant cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrolment), unstable angina, congestive heart failure (New York Heart Association Classification Class > II) or serious uncontrolled cardiac Arrhythmia requiring medication Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance <60 mL / min). Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin > 1.5 upper limit of normal). Impaired hematopoietic function (leucocytes <4000 / mm3, neutrophils <1500 / mm 3, platelets <100000 / mm3). Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 <50% or DLCO <40% of normal age value). History or presence of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of HIPEC or chemotherapy or patient at high risk from treatment complications. Pregnancy. Krukenberg tumor Refusal to join the study.

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
Interventional Model Description: This is a phase III randomized, multicenter study with two different arm: experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin comparator: standard surgery
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin | Procedure: Surgery plus HIPEC CO2<br>* Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin v<br>|
| Active Comparator: Comparator<br>Standard surgery | Procedure: Standard surgery<br>* Standard surgery without HIPEC CO2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | The primary efficacy endpoint is DFS defined as the time from randomization to the date of first local relapse or distant relapse or peritoneal carcinomatosis or death for any cause, whichever comes first. | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival (OS) defined as the time from randomization to the death for any cause | This outcome measure will be assessed approximately 3 years after the last patient enrolled, at the same time points of the Primary Endpoint | 
| Local recurrence free survival | Local recurrence free survival (LRFS) defined as the time from randomization defined as the time from randomization to the date of first local relapse, peritoneal carcinomatosis or death for any cause, whichever comes first. | This outcome measure will be assessed approximately 3 years after the last patient enrolled, at the same time points of the Primary Endpoint | 
| morbidity evaluated during and after surgery | morbidity evaluated during and after surgery graded according to the NCI-CTAE version 4.03 for AE related to chemotherapy and according to Clavien Dindo for surgery complications | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 
| post-surgery complication | number of post-surgery complication | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 
| duration of surgery | timing of surgery | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 
| length of hospitalization | duration of hospitalization | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 
| mortality at 30 and 90 days from surgery | mortality at 30 and 90 days from surgery | This outcome measure will be assessed at 30 and 90 days from surgery | 
| patients performing the adjuvant chemotherapy. | number of patients performing the adjuvant chemotherapy. | This outcome measure will be assessed approximately 3 years after the last patient enrolled | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastric cancer, HIPEC CO2, Prophylactic surgery, hyperthermic intraperitoneal chemotherapy