Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach

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

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.

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.

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-3-4. 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):

  • Haematology (Neutrophils > 2.0 x 109 /L, Platelet > 100 x 109 /L, Hemoglobin > 10g/dL);
  • Hepatic function (Total bilirubin < 1 UNL, ASAT (SGOT) and ALAT (SGPT) < 2.5xUNL, Alkaline phosphatase < 2.5xUNL. Patients with ASAT or ALAT > 1.5xUNL associated with alkaline phosphatase > 2.5XUNL are not eligible.)
  • Renal function (Creatinine < 1.5 UNL. In presence of borderline values, the calculated creatinine clearance according to Cockroft-Gault formula, 60 ML/min.

• Recovery from acute effects of surgery. The first infusion of study chemotherapy should be administered 3 to 8 weeks after surgery treatment;

• Written informed consent signed and dated before randomization procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirement.

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;

• Presence of other systemic disease limiting drug administration and influencing patient survival:

  • uncontrolled hypertension,
  • high-risk uncontrolled arrhythmia,
  • unstable angina pectoris;

• Symptomatic

  • peripheral neuropathy,
  • altered hearing > 2 grade by NCIC-CTG criteria;

• Active uncontrolled infection.

• Definite contra-indications for the use of corticosteroids: unstable diabetes mellitus, active peptic ulcer;

• Concurrent administration of:

  • corticosteroids or equivalent except as use for the prophylactic medication regimen, treatment of acute hypersensitivity reactions or unless chronic treatment (initiated > 6 months prior to study entry) at low doses (< 20mg methylprednisolone or equivalent);
  • any other experimental drug under investigation: concurrent treatment with any other anticancer therapy, growth factors with preventive intent