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

Stomach Neoplasms Clinical Trial

— GOETH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03917173
• Other study ID #: IRFMN-GCC-7813
• Secondary ID: 2019-001478-27
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2020
• Est. completion date: June 1, 2025

Study information

• Verified date: October 2023
• Source: Mario Negri Institute for Pharmacological Research
• Contact: Andrea Di Giorgio, MD
• Phone: 003906 3015
• Email: andrea.digiorgio[@]policlinicogemelli.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Stomach Neoplasms

Intervention

Procedure:
• Surgery plus HIPEC CO2
Prophylactic surgery plus HIPEC CO2 performed with mitomycin and cisplatin v
• Standard surgery
Standard surgery without HIPEC CO2

Locations

Country	Name	City	State
Italy	IRCCS Istituto Tumori Giovanni Paolo II	Bari
Italy	AO Santa Croce e Carle	Cuneo
Italy	ULLS1 1 Dolomiti - Ospedale di Feltre	Feltre
Italy	Policlinico di Milano	Milano
Italy	A.O.R.N. A.Cardarelli	Napoli
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Ospedale Evangelico Betania	Napoli
Italy	Azienda Ospedaliera S. Camillo Forlanini	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Italy	Fondazione Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore	Roma
Italy	IRCCS Policlinico San Donato	San Donato Milanese
Italy	IRCCS Casa Sollievo della Sofferenza	San Giovanni Rotondo

Sponsors (1)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	post-surgery complication	number of post-surgery complication	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	duration of surgery	timing of surgery	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	length of hospitalization	duration of hospitalization	This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary	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
Secondary	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