SURGIGAST: Surgical Resection Plus Chemotherapy Versus Chemotherapy Alone in Oligometastatic Stage IV Gastric Cancer

Sponsor

University Hospital, Lille (Other)

Overall Status

Recruiting

CT.gov ID

NCT03042169

Collaborator

National Cancer Institute, France (Other)

424

Enrollment

Location

Arms

17.2

Anticipated Duration (Months)

24.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Surgical resection of the primary tumour and treatment of the metastatic site in oligometastatic stage IV metastatic gastric adenocarcinoma enhances survival and improves quality of life with acceptable postoperative morbidity and mortality in a selected group of operable patients with only one metastatic site that does not progress under chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma	Drug: Preoperative Chemotherapy Procedure: Surgery Drug: Postoperative chemotherapy	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

424 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Surgical Resection Plus Chemotherapy Versus Chemotherapy Alone in Oligometastatic Stage IV Gastric Cancer - a Multicenter, Prospective, Open-labeled, Two-armed, Randomized, Controlled Phase III Trial

Actual Study Start Date :

Aug 25, 2021

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: continuation of chemotherapy Patients assigned to arm A will continue to receive the same chemotherapy regimen they received before randomization. Chemotherapy should be restarted between D1 and D30 after randomization. In case of poor tolerance to the induction chemotherapy, alternative chemotherapy regimen might be discussed, according to local standards and national guidelines (www.tncd.org).	Drug: Preoperative Chemotherapy Standard chemotherapy regiments according to risk of recurrence Drug: Postoperative chemotherapy Chemotherapy should be restarted between D1 and D30 post-randomization
Experimental: surgical removal of the primary tumour and treatment of the metastatic site followed by chemotherapy Patients assigned to arm B will undergo gastrectomy (subtotal or total according to the location of the primary tumour) between D1 and D30 after randomization. Subtotal gastrectomy is recommended if it allows a complete resection of the primary tumour to limit postoperative morbidity in such metastatic situations, based on the results of REGATTA	Procedure: Surgery the surgical treatment will undergo gastrectomy between D1 and D30 after randomization. Other Names: surgical removal of the primary tumour followed by chemotherapy Drug: Postoperative chemotherapy Chemotherapy should be restarted between D1 and D30 post-randomization

Arm

Intervention/Treatment

Active Comparator: continuation of chemotherapy

Patients assigned to arm A will continue to receive the same chemotherapy regimen they received before randomization. Chemotherapy should be restarted between D1 and D30 after randomization. In case of poor tolerance to the induction chemotherapy, alternative chemotherapy regimen might be discussed, according to local standards and national guidelines (www.tncd.org).

Drug: Preoperative Chemotherapy

Standard chemotherapy regiments according to risk of recurrence

Drug: Postoperative chemotherapy

Chemotherapy should be restarted between D1 and D30 post-randomization

Experimental: surgical removal of the primary tumour and treatment of the metastatic site followed by chemotherapy

Patients assigned to arm B will undergo gastrectomy (subtotal or total according to the location of the primary tumour) between D1 and D30 after randomization. Subtotal gastrectomy is recommended if it allows a complete resection of the primary tumour to limit postoperative morbidity in such metastatic situations, based on the results of REGATTA

Procedure: Surgery

the surgical treatment will undergo gastrectomy between D1 and D30 after randomization.

Other Names:

surgical removal of the primary tumour followed by chemotherapy

Drug: Postoperative chemotherapy

Chemotherapy should be restarted between D1 and D30 post-randomization

Outcome Measures

Primary Outcome Measures

Overall survival [Between the date of randomisation to the date of death whatever the cause,assessed up to 2 years]

Secondary Outcome Measures

EORTC QLQ C30 [Every 3 months during 2 years]
QLQ STO 22 questionnaires [Every 3 months during 2 years]
Progression free survival [from randomisation to the date of documented progression according to RECIST or death whatever the cause,assessed up to 2 years]
Surgery related postoperative morbidity-mortality [within 30 days and 90 days]
grade III, IV and V and complications according to the Dindo-Clavien classification
Specific complications related to treatment of the metastatic site [within 30 days and 90 days post-treatment]
grade III, IV and V complications according to the Dindo-Clavien classification for surgical treatment strategy and grade III, IV and V adverse reactions according to the NCI-CTCAE v5.0 for other treatment strategies (i.e. HIPEC, radiofrequency, microwave and radiotherapy).
Chemotherapy related toxicities : grade III, IV and V toxicities according to the NCI-CTCAE v5.0 [Every 3 months during 2 years]]
Overall cumulative duration of hospitalisation [throughout the duration of the study, during 2 years]
calculated in days from randomization
Number of interventional palliative procedures per patient [throughout the duration of the study, during 2 years]
mean per patient from randomization

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Primary diagnosis of UICC stage IV gastric adenocarcinoma with histological proof of the primary tumour (with HER2 status, PCC histology and MMR status available and SRC histology available on anatomo-pathology reports)
Without any form of previous treatment (surgery and / or chemotherapy and / or radiotherapy) for this diagnosis other than local endoscopic treatment. Note : 3. pPatients having received first line chemotherapy for at least 2 months and completing inclusion/exclusion criteria can be included in the study at V2
Locally resectable primary tumour and oligometastatic lesion accessible to surgical resection or local ablation procedure
Oligometastatic lesion : Retro-Peritoneal Lymph Node Metastases (RPLM) and/or another metastatic lesion on only one organ (solid organ, lymph node or limited localised peritoneal carcinomatosis with PCI < 7) according to the following non-exhaustive list of definitions:
RPLM: para-aortal, intra-aorto-caval, para-pancreatic or mesenteric lymph node(s). Note: in duodenum invading gastric cancer, retro-pancreatic nodes are not regarded as metastatic sites
Other acceptable limited metastatic lesions:

Localized potentially operable peritoneal carcinomatosis: PCI < 7 including uni or bilateral Krukenberg tumors (ovarian metastases)
Liver: maximum of 5 metastatic lesions that are potentially resectable
Lung: unilateral involvement, potentially resectable
Uni- or bilateral adrenal gland metastases
Extra-abdominal lymph node metastases such as supraclavicular or cervical lymph node involvement
Localized bone involvement (defined as being within one radiation field) Notes: 1. Patients with more than one metastatic site in only one organ are eligible. 2. In case of doubt for considering whether a metastatic site is limited or not, please submit the case with relevant anonymised information to the medical coordinator of the study for approval. 6. Only one solid organ metastatic site (hepatic, lung, adrenal gland, bone, brain...). Patients with more than one metastatic lesion in only one organ are eligible

ECOG performance status 0 or 1
Man or women aged ≥ 18 years and ≤ 80 years
For surgery and/or chemotherapy, adequate cardiac, respiratory, bone marrow, renal and liver functions according to usual practices standards
Ability to understand and complete quality of life questionnaires (EORTC QLQ C30 and QLQ STO 22)
Negative pregnancy test (urine or serum) performed prior to start the study in for females of childbearing potential with reproductive potential
Male and female patients of child-bearing reproductive potential must agree to us an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after the end of study treatment
Patient covered by a government Health Insurance
Patient who provides a signed written Inform Consent

Exclusion Criteria:

Other histological subtype than adenocarcinoma
ECOG performance status ≥ 2 2,3 or 4
Diffuse peritoneal carcinomatosis (PCI ≥ 7) or significant ascites
Metastatic disease involving more than one solid organ metastatic site
Primary tumor irresectability and/or metastatic lesion not accessible for resection or local ablation procedure or need for multi-visceral resection with expected high complication rate
Contraindication to chemotherapy or surgery according to the multidisciplinary team decision
Second uncontrolled malignant tumour
Proximal (junctionnal) tumour growth across the Z-line requiring additional trans thoracic oesophageal resectionµ
Emergency surgery due to bleeding or perforation
Age > 80 years
Weight loss ≥ 20% persisting despite appropriate nutritional assistance
Severe comorbid conditions that may jeopardize short term outcomes (e.g. cardiac, respiratory, bone marrow, renal or liver insufficiency...)
Dihydropyrimidine dehydrogenase Deficiency (DPD)
Women who are pregnant or breastfeeding
Patients in emergency situations
Patients kept in detention and/or under legal protection under psychiatric care and/or interned in a social or psychiatric institution
Adult patient under legal protection or in the incapacity to express his/her consent
Patient not covered by a health insurance system