Clinical trial NCT03042169: Surgical Resection Plus Chemotherapy Versus Chemotherapy Alone in Oligometastatic Stage IV Gastric Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Gastric Adenocarcinoma
Keywords: Stage IV gastric cancer
palliative surgery
chemotherapy
survival
quality of life
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2017-02-03
Enrollment: 424
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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)
2. 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
3. Locally resectable primary tumour and oligometastatic lesion accessible to surgical resection or local ablation procedure
4. 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:

   1. 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
   2. 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
5. ECOG performance status 0 or 1
6. Man or women aged ≥ 18 years and ≤ 80 years
7. For surgery and/or chemotherapy, adequate cardiac, respiratory, bone marrow, renal and liver functions according to usual practices standards
8. Ability to understand and complete quality of life questionnaires (EORTC QLQ C30 and QLQ STO 22)
9. Negative pregnancy test (urine or serum) performed prior to start the study in for females of childbearing potential with reproductive potential
10. 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
11. Patient covered by a government Health Insurance
12. Patient who provides a signed written Inform Consent

Exclusion Criteria:

1. Other histological subtype than adenocarcinoma
2. ECOG performance status ≥ 2 2,3 or 4
3. Diffuse peritoneal carcinomatosis (PCI ≥ 7) or significant ascites
4. Metastatic disease involving more than one solid organ metastatic site
5. 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
6. Contraindication to chemotherapy or surgery according to the multidisciplinary team decision
7. Second uncontrolled malignant tumour
8. Proximal (junctionnal) tumour growth across the Z-line requiring additional trans thoracic oesophageal resectionµ
9. Emergency surgery due to bleeding or perforation
10. Age \> 80 years
11. Weight loss ≥ 20% persisting despite appropriate nutritional assistance
12. Severe comorbid conditions that may jeopardize short term outcomes (e.g. cardiac, respiratory, bone marrow, renal or liver insufficiency...)
13. Dihydropyrimidine dehydrogenase Deficiency (DPD)
14. Women who are pregnant or breastfeeding
15. Patients in emergency situations
16. Patients kept in detention and/or under legal protection under psychiatric care and/or interned in a social or psychiatric institution
17. Adult patient under legal protection or in the incapacity to express his/her consent
18. Patient not covered by a health insurance system

Primary outcomes:
measure: Overall survival
timeFrame: Between the date of randomisation to the date of death whatever the cause,assessed up to 2 years
Secondary outcomes:
measure: EORTC QLQ C30
timeFrame: Every 3 months during 2 years
measure: QLQ STO 22 questionnaires
timeFrame: Every 3 months during 2 years
measure: Progression free survival
timeFrame: from randomisation to the date of documented progression according to RECIST or death whatever the cause,assessed up to 2 years
measure: Surgery related postoperative morbidity-mortality
timeFrame: within 30 days and 90 days
measure: Specific complications related to treatment of the metastatic site
timeFrame: within 30 days and 90 days post-treatment
measure: Chemotherapy related toxicities : grade III, IV and V toxicities according to the NCI-CTCAE v5.0
timeFrame: Every 3 months during 2 years]
measure: Overall cumulative duration of hospitalisation
timeFrame: throughout the duration of the study, during 2 years
measure: Number of interventional palliative procedures per patient
timeFrame: throughout the duration of the study, during 2 years
Other outcomes:
Locations:
city: Saint-Herblain
country: France
facility: Ico - Site Gauducheau - St Herblain
Study officials:
affiliation: University Hospital, Lille
name: Guillaume Piessen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: