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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stomach Neoplasms
• Intervention / Treatment: Procedure: Standard surgery; Procedure: Surgery plus HIPEC CO2

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Di Giorgio, MD; Phone Number: 7255 003906 3015; Email: andrea.digiorgio@policlinicogemelli.it
• Study Contact Backup: Name: Erica Rulli; Phone Number: 4684 0039023901; Email: erica.rulli@marionegri.it

Study Locations

• Italy
  • Bari, Italy
    • Active, not recruiting
    • Irccs Istituto Tumori Giovanni Paolo Ii
  • Cuneo, Italy
    • Active, not recruiting
    • AO Santa Croce e Carle
  • Feltre, Italy
    • Active, not recruiting
    • ULLS1 1 Dolomiti - Ospedale di Feltre
  • Milano, Italy
    • Active, not recruiting
    • Policlinico di Milano
  • Napoli, Italy
    • Active, not recruiting
    • Azienda Ospedaliera Universitaria Federico II
  • Napoli, Italy
    • Active, not recruiting
    • Ospedale Evangelico Betania
  • Napoli, Italy
    • Active, not recruiting
    • A.O.R.N. A.Cardarelli
  • Roma, Italy
    • Active, not recruiting
    • Azienda Ospedaliera S. Camillo Forlanini
  • Roma, Italy
    • Active, not recruiting
    • Fondazione Policlinico Universitario A. Gemelli
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario A. Gemelli
    • Contact: Alberto Biondi
  • Roma, Italy
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
    • Contact: Andrea Di Giorgio, MD
  • San Donato Milanese, Italy
    • Active, not recruiting
    • IRCCS Policlinico San Donato
  • San Giovanni Rotondo, Italy
    • Active, not recruiting
    • IRCCS Casa Sollievo della Sofferenza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin	Procedure: Surgery plus HIPEC CO2; Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin v
Active Comparator: Comparator; Standard surgery	Procedure: Standard surgery; Standard surgery without HIPEC CO2

What is the study measuring?

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
duration of surgery	timing of surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled
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
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

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Investigators: Principal Investigator: Andrea Di Giorgio, Fondazione Policlinico Universitario Agostino Gemelli Irccs

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: gastric cancer; hyperthermic intraperitoneal chemotherapy; Prophylactic surgery; HIPEC CO2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: IRFMN-GCC-7813; 2019-001478-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No