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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 :
- •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:
- •Patients with more than one metastatic site in only one organ are eligible.
- •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.
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: Preoperative Chemotherapy (Drug)
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).
干预措施: Postoperative chemotherapy (Drug)
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
干预措施: Surgery (Procedure)
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
干预措施: Postoperative chemotherapy (Drug)
结局指标
主要结局
Overall survival
时间窗: Between the date of randomisation to the date of death whatever the cause,assessed up to 2 years
次要结局
- 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)
- Specific complications related to treatment of the metastatic site(within 30 days and 90 days post-treatment)
- 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)
- Number of interventional palliative procedures per patient(throughout the duration of the study, during 2 years)
- EORTC QLQ C30(Every 3 months during 2 years)