Clinical trial NCT03917173: Prophylactic Surgery Plus HIPEC With CO2 in Patients Affected by Gastric Carcinoma.GOETH Study
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stomach Neoplasms
Keywords: gastric cancer
HIPEC CO2
Prophylactic surgery
hyperthermic intraperitoneal chemotherapy
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease free survival
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
Secondary outcomes:
measure: Overall Survival
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled, at the same time points of the Primary Endpoint
measure: Local recurrence free survival
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled, at the same time points of the Primary Endpoint
measure: morbidity evaluated during and after surgery
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: post-surgery complication
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: duration of surgery
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: length of hospitalization
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
measure: mortality at 30 and 90 days from surgery
timeFrame: This outcome measure will be assessed at 30 and 90 days from surgery
measure: patients performing the adjuvant chemotherapy.
timeFrame: This outcome measure will be assessed approximately 3 years after the last patient enrolled
Other outcomes:
Locations:
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
city: Cuneo
country: Italy
facility: AO Santa Croce e Carle
city: Feltre
country: Italy
facility: ULLS1 1 Dolomiti - Ospedale di Feltre
city: Milano
country: Italy
facility: Policlinico di Milano
city: Napoli
country: Italy
facility: A.O.R.N. A.Cardarelli
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Napoli
country: Italy
facility: Ospedale Evangelico Betania
city: Roma
country: Italy
facility: Azienda Ospedaliera S. Camillo Forlanini
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli Irccs Universita' Cattolica Del Sacro Cuore
city: San Donato Milanese
country: Italy
facility: IRCCS Policlinico San Donato
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Casa Sollievo della Sofferenza
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Andrea Di Giorgio
role: PRINCIPAL_INVESTIGATOR
References: