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

Not Applicable

Recruiting

• Conditions: Stomach Neoplasms
• Interventions: Procedure: Standard surgery; Procedure: Surgery plus HIPEC CO2

• Registration Number: NCT03917173
• Lead Sponsor: Mario Negri Institute for Pharmacological Research

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-04-02
• Study First Submitted QC: 2019-04-15
• Study First Posted: 2019-04-16
• Study Start: 2020-06-01
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-26
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

1. Patients with histologically documented gastric carcinoma (diffuse/intestinal histotype) eligibile for R0.

   1. Presurgical or intraoperative stage T3-T4 N0-N+ primary tumour (TNM 8 th).
   2. Urgent presentation: perforation without purulent generalized peritonitis
   3. Positive cytology of peritoneal fluid (if previously obtained)

2. Age ≥ 18 years and ≤75 years.

3. Written informed consent.

Exclusion Criteria

1. Gastroesophageal Junction (GEJ) cancer
2. Distant metastatic disease (even if limited and completely resected)
3. Peritoneal carcinomatosis
4. 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).
5. Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
6. Poor general conditions (ECOG > 2).
7. 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
8. Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance <60 mL / min).
9. Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin > 1.5 upper limit of normal).
10. Impaired hematopoietic function (leucocytes <4000 / mm3, neutrophils <1500 / mm 3, platelets <100000 / mm3).
11. Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 <50% or DLCO <40% of normal age value).
12. 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.
13. Pregnancy.
14. Krukenberg tumor
15. Refusal to join the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Comparator	Standard surgery	Standard surgery
Experimental	Surgery plus HIPEC CO2	Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin

Primary Outcome Measures

Name	Time	Method
Disease free survival	This outcome measure will be assessed approximately 3 years after the last patient enrolled	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	This outcome measure will be assessed approximately 3 years after the last patient enrolled, at the same time points of the Primary Endpoint	Overall Survival (OS) defined as the time from randomization to the death for any cause
Local recurrence free survival	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 (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.
morbidity evaluated during and after surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled	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
post-surgery complication	This outcome measure will be assessed approximately 3 years after the last patient enrolled	number of post-surgery complication
patients performing the adjuvant chemotherapy.	This outcome measure will be assessed approximately 3 years after the last patient enrolled	number of patients performing the adjuvant chemotherapy.
duration of surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled	timing of surgery
length of hospitalization	This outcome measure will be assessed approximately 3 years after the last patient enrolled	duration of hospitalization
mortality at 30 and 90 days from surgery	This outcome measure will be assessed at 30 and 90 days from surgery	mortality at 30 and 90 days from surgery

Trial Locations

Locations (12)

IRCCS Istituto Tumori Giovanni Paolo II; 🇮🇹 Bari, Italy

ULLS1 1 Dolomiti - Ospedale di Feltre; 🇮🇹 Feltre, Italy

A.O.R.N. A.Cardarelli; 🇮🇹 Napoli, Italy

Fondazione Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore; 🇮🇹 Roma, Italy

AO Santa Croce e Carle; 🇮🇹 Cuneo, Italy

Policlinico di Milano; 🇮🇹 Milano, Italy

Fondazione Policlinico Universitario A. Gemelli; 🇮🇹 Roma, Italy

Azienda Ospedaliera S. Camillo Forlanini; 🇮🇹 Roma, Italy

Azienda Ospedaliera Universitaria Federico II; 🇮🇹 Napoli, Italy

Ospedale Evangelico Betania; 🇮🇹 Napoli, Italy

IRCCS Policlinico San Donato; 🇮🇹 San Donato Milanese, Italy

IRCCS Casa Sollievo della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy