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Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S)

This study has been completed.
Sponsor:
Collaborators:
Aventis Pharmaceuticals
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Gruppo Oncologico Italiano di Ricerca Clinica
Gruppo Oncologico del Nord-Ovest
Italian Trial in Medical Oncology
Southern Italy Cooperative Oncology Group
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Oncotech
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier:
NCT01640782
First received: July 9, 2012
Last updated: July 17, 2014
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Stomach
Adenocarcinoma of the Gastroesophageal Junction
Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin
Drug: Leucovorin, 5-Fluorouracil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mario Negri Institute for Pharmacological Research:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Toxicity, graded according to the NCI-CTG Expanded Common Toxicity Criteria [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 1100
Study Start Date: February 2005
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sequential regimen
Sequential treatment with CPT-11 plus Fluorouracil (FU), folinic acid (LV) and Docetaxel (TXT) plus Cisplatin (CDDP)
Drug: Irinotecan, Leucovorin, 5-Fluorouracil, Docetaxel, Cisplatin
  • Irinotecan (CPT-11) 180 mg/m2, given as 60 min. i.v. infusion on day 1 every 2 weeks followed by
  • Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by
  • 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 4 administrations.

After 3 weeks from last infusion:

  • Docetaxel (TXT) 75 mg/m2, given as a 1h i.v. infusion on day 1 followed by
  • Cisplatin (CDDP) 75 mg/m2, given as a 1h i.v. infusion on.day 1, every 3 weeks, for 3 cycles.
Active Comparator: De Gramont regimen
Fluorouracil (5-FU), folinic acid (LV)
Drug: Leucovorin, 5-Fluorouracil
  • Leucovorin (LV) 100 mg/m2, given as a 2h i.v. infusion on days 1 and 2 every 2 weeks followed by
  • 5-Fluorouracil (5-FU) 400 mg/m2 given as bolus, and then 5-Fluorouracil (5-FU) 600 mg/m2 given as a 22h continuous infusion on days 1 and 2, every 2 weeks for 9 administrations.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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-3-4. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01640782

  Show 101 Study Locations
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
Aventis Pharmaceuticals
Gruppo Italiano per lo studio dei Carcinomi dell'Apparato Digerente
Gruppo Oncologico Italiano di Ricerca Clinica
Gruppo Oncologico del Nord-Ovest
Italian Trial in Medical Oncology
Southern Italy Cooperative Oncology Group
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Oncotech
Investigators
Principal Investigator: Emilio Bajetta, MD Istituto Nazionale Per lo Studio e la Cura dei Tumori Milano
  More Information

No publications provided by Mario Negri Institute for Pharmacological Research

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01640782     History of Changes
Other Study ID Numbers: ITACA-S
Study First Received: July 9, 2012
Last Updated: July 17, 2014
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Mario Negri Institute for Pharmacological Research:
adenocarcinoma of the stomach
adenocarcinoma of the gastroesophageal junction

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Cisplatin
Docetaxel
Fluorouracil
Irinotecan
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on November 23, 2014