Open Label, Randomised, Multicenter Phase III Study of Adjuvant Chemotherapy in Radically Resected Adenocarcinoma of the Stomach or Gastroesophageal Junction: Comparison of a Sequential Treatment (CPT-11+5-FU/LV --> TXT+CDDP) Versus a 5-FU/LV Regimen
Overview
- Phase
- Phase 3
- Intervention
- Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin
- Conditions
- Adenocarcinoma of the Stomach
- Sponsor
- Mario Negri Institute for Pharmacological Research
- Enrollment
- 1100
- Locations
- 101
- Primary Endpoint
- Progression Free Survival will be defined as the time from date of randomisation to date of first appearance of local, regional or distant relapse, or death from any cause; patients alive without relapse will be censored at date last known to be alive.
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Open label, randomised, multicenter, superiority study for efficacy. Patients with histologically proven adenocarcinoma of the stomach or gastroesophageal junction without gross or microscopic evidence of residual disease after surgery with curative intent and fulfilling all the inclusion/exclusion criteria are eligible for this study.
Detailed Description
Open label, randomised, multicenter, superiority study for efficacy. Patients with histologically proven adenocarcinoma of the stomach or gastroesophageal junction without gross or microscopic evidence of residual disease after surgery with curative intent and fulfilling all the inclusion/exclusion criteria are eligible for this study. Allocation to treatment will be done centrally using a randomisation scheme and will be stratified by center and nodal involvement (N- vs. N+). Access to random system will be allowed by phone or via web. All included patients in both groups will received fixed period of 18 weeks of treatment unless unacceptable toxicity or disease relapse during treatment. After cessation of therapy, patients will have a follow-up period while not receiving further treatment. After relapse further chemotherapy is left to the investigator's judgement. When the last patient is randomised, follow-up will be truncated at the achievement of the required number of events. Time to progression and time to death are the main study outcomes. During the course of the trial, an independent Data and Safety Monitoring Board (DSMB) will advise the Steering Committee on efficacy and/or safety aspects of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically proven adenocarcinoma of the stomach or gastroesophageal junction without gross or microscopic evidence of residual disease after surgery with curative intent;
- •Subtotal or total gastrectomy with at least D1 dissection;
- •Gastroesophageal junction adenocarcinoma extending to the stomach with the center lying 2 to 5 cm below the anatomic esophago-gastric junction;
- •Patients with nodal involvement (pN+) or patients without nodal involvement (pN0) with pT2b-3-
- •It is recommended to examine at least 15 lymph nodes;
- •Age between 18 and 75 years;
- •ECOG performance status 0-1;
- •No previous chemotherapy and/or radiotherapy;
- •Complete staging procedures within 3 months prior to randomization;
- •Laboratory requirement (within 8 days prior to randomization):
Exclusion Criteria
- •Non-radical surgery as assessed microscopically (no tumor-free margin of resection, positive biopsy of peritoneal suspicious lesions);
- •Synchronous metastases, even curatively resected;
- •Pregnant or lactating patients; patients with reproductive potential must implement adequate contraceptive measures;
- •Prior or concurrent history of:
- •positive HIV serology,
- •chronic diarrhoea,
- •chronic bowel inflammation or subobstruction,
- •neoplasm other than gastric cancer, except for: curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix,
- •previous history of myocardial infarction within 1 year from study entry,
- •hypersensitivity reaction to polysorbate 80;
Arms & Interventions
Sequential regimen
Sequential treatment with CPT-11 plus Fluorouracil (FU), folinic acid (LV) and Docetaxel (TXT) plus Cisplatin (CDDP)
Intervention: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin
De Gramont regimen
Fluorouracil (5-FU), folinic acid (LV)
Intervention: Leucovorin, 5-Fluorouracil
Outcomes
Primary Outcomes
Progression Free Survival will be defined as the time from date of randomisation to date of first appearance of local, regional or distant relapse, or death from any cause; patients alive without relapse will be censored at date last known to be alive.
Time Frame: 3 years
Secondary Outcomes
- OS will be defined as the time from date of randomisation to date of death by any cause, with living patients censored at date last known to be alive(3 years)
- Adverse events(3 years)
- Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria(3 years)