Prospective Multicentric Randomized Study of Glivec® in Advanced GIST Expressing C-kit: Interruption After 5 Years vs Maintenance

This study has been completed.
Sponsor:
Collaborator:
Gustave Roussy, Cancer Campus, Grand Paris
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT00367861
First received: August 21, 2006
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

Gastrointestinal stromal tumors (GISTs) are associated with a dismal prognosis in localized and advanced phase with a major resistance to conventional chemotherapy agents. Virtually all malignant GISTs actually harbor activating mutations of the KIT pathway in the tumor cells, leading to ligand-independent activation of KIT tyrosine kinase activity and tumor growth in vitro. Glivec® inhibits KIT and exerts a major antitumor efficacy in vivo in patients with advanced GIST. Glivec® is generally pursued until progression or intolerance. The optimal duration of treatment with Glivec® remains unknown. The objective of this study is to determine the feasibility of Glivec® treatment interruption with reintroduction at progression in GIST patients.


Condition Intervention Phase
Sarcoma
Gastro-intestinal Stromal Tumors (GIST)
Drug: interruption of Glivec®
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: A Prospective Multicentric Randomized Study of Glivec® in Patients With Advanced Gastrointestinal Stromal Tumors Expressing C-kit Comparing Treatment Interruption After 5 Years vs Treatment Maintenance

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    to compare progression free survival beyond 2 years in patients treated by Glivec® achieving a CR, PR or SD at 5 years. Patients will be randomized either interruption of Glivec® until progression w/RECIST criteria and the re-start (group 1) or(/vs) maintenance of Glivec® (group 2).


Secondary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare overall survival beyond 2 years in the two groups of randomized patients.

  • Toxicity [ Time Frame: 7 years ] [ Designated as safety issue: No ]
    Evaluation of toxicity during inclusion in the study


Enrollment: 564
Study Start Date: May 2002
Study Completion Date: May 2013
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: interruption of Glivec® Drug: interruption of Glivec®
interruption of Glivec®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients 18 years of age or over.
  2. Histologically documented diagnosis of malignant GIST.
  3. Immunohistochemical documentation of c-kit (CD117) expression either by the primary tumor or metastases using the DAKO assay.
  4. Performance status 0,1, 2, 3 (ECOG)
  5. Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN, SGOT and SGPT < 2.5 x UNL (or < 5 x ULN if hepatic metastases are present), creatinine < 1.5 x ULN, ANC > 1.0 x 109/L, platelets > 100 x 109/L.
  6. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 2 weeks (according to updated Invest. Brochure) following discontinuation of study drug.
  7. Written, voluntary, informed consent.

Exclusion Criteria:

  1. Patient has another malignant tumor in CR<3 years (except if the other primary malignancy is inactive and not requiring active intervention). Previous basal cell skin cancer or a cervical carcinoma in situ are allowed.
  2. Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
  3. Female patients who are pregnant or breast-feeding.
  4. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  5. Patients received chemotherapy within 2 weeks prior to study entry, unless the disease is rapidly progressing
  6. Patients had a major surgery within 2 weeks prior to entry study
  7. Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
  8. Previous treatment with Glivec®
  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: NCT00367861

Locations
France
Institut Bergonié
Bordeaux, France, 33000
Centre Oscar Lambret
Lille, France, 59000
Centre Leon Berard
Lyon, France, 69008
Hopital Edouard Herriot
Lyon, France, 69008
Hopitaux de La Timone
Marseille, France, 13000
Institut Paoli Calmette
Marseilles, France, 13000
Centre Alexis Vautrin
Nancy, France, 57000
Institut Gustave Roussy
Villejuif, France, 94850
Sponsors and Collaborators
Centre Leon Berard
Gustave Roussy, Cancer Campus, Grand Paris
Investigators
Principal Investigator: Jean Yves Blay, M.D., Ph.D Centre Leon Berard, INSERM U590 & Hopital Edouard Herriot
Principal Investigator: Axel Le Cesne, M.D. Gustave Roussy, Cancer Campus, Grand Paris
  More Information

Publications:

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT00367861     History of Changes
Other Study ID Numbers: CST1571BFR14, ET2002-021
Study First Received: August 21, 2006
Last Updated: February 21, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:
GIST
Glivec®
randomized
phase III

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014