NCT00367861

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
564

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started May 2002

Longer than P75 for phase_3

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2002

Completed
4.3 years until next milestone

First Submitted

Initial submission to the registry

August 21, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 23, 2006

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2013

Completed
Last Updated

February 24, 2014

Status Verified

February 1, 2014

Enrollment Period

9.9 years

First QC Date

August 21, 2006

Last Update Submit

February 21, 2014

Conditions

SarcomaGastro-intestinal Stromal Tumors (GIST)

Keywords

GISTGlivec®randomizedphase III

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    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).

    2 years

Secondary Outcomes (2)

  • Overall survival

    2 years

  • Toxicity

    7 years

Study Arms (1)

interruption of Glivec®

EXPERIMENTAL
Drug: interruption of Glivec®

Interventions

interruption of Glivec®DRUG

interruption of Glivec®

interruption of Glivec®

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients 18 years of age or over.
  • Histologically documented diagnosis of malignant GIST.
  • Immunohistochemical documentation of c-kit (CD117) expression either by the primary tumor or metastases using the DAKO assay.
  • Performance status 0,1, 2, 3 (ECOG)
  • 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.
  • 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.
  • Written, voluntary, informed consent.

You may not qualify if:

  • 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.
  • 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)
  • Female patients who are pregnant or breast-feeding.
  • Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  • Patients received chemotherapy within 2 weeks prior to study entry, unless the disease is rapidly progressing
  • Patients had a major surgery within 2 weeks prior to entry study
  • Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
  • Previous treatment with Glivec®

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hopital Edouard Herriot

Lyon, 69008, France

Location

Hopitaux de La Timone

Marseille, 13000, France

Location

Institut Paoli Calmette

Marseille, 13000, France

Location

Centre Alexis Vautrin

Nancy, 57000, France

Location

Institut Gustave Roussy

Villejuif, 94850, France

Location

Related Publications (7)

  • Le Cesne A, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Cioffi A, Emile JF, Chabaud S, Perol D, Blay JY; French Sarcoma Group. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):942-9. doi: 10.1016/S1470-2045(10)70222-9. Epub 2010 Sep 21.

    PMID: 20864406BACKGROUND

  • Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, Adenis A, Viens P, Rios M, Bompas E, Cupissol D, Guillemet C, Kerbrat P, Fayette J, Chabaud S, Berthaud P, Perol D. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007 Mar 20;25(9):1107-13. doi: 10.1200/JCO.2006.09.0183.

    PMID: 17369574BACKGROUND

  • Patrikidou A, Chabaud S, Ray-Coquard I, Bui BN, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Domont J, Perol D, Blay JY, Le Cesne A; French Sarcoma Group. Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial. Ann Oncol. 2013 Apr;24(4):1087-93. doi: 10.1093/annonc/mds587. Epub 2012 Nov 21.

    PMID: 23175622BACKGROUND

  • Blesius A, Cassier PA, Bertucci F, Fayette J, Ray-Coquard I, Bui B, Adenis A, Rios M, Cupissol D, Perol D, Blay JY, Le Cesne A. Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial. BMC Cancer. 2011 Feb 15;11:72. doi: 10.1186/1471-2407-11-72.

    PMID: 21324142BACKGROUND

  • Blay JY, Perol D, Le Cesne A. Imatinib rechallenge in patients with advanced gastrointestinal stromal tumors. Ann Oncol. 2012 Jul;23(7):1659-65. doi: 10.1093/annonc/mdr622. Epub 2012 Feb 21.

    PMID: 22357253BACKGROUND

  • Blay JY, Devin Q, Duffaud F, Toulmonde M, Firmin N, Collard O, Bompas E, Verret B, Ray-Coquard I, Salas S, Henon C, Honore C, Brahmi M, Dufresne A, Pracht M, Hervieu A, Penel N, Bertucci F, Rios M, Saada-Bouzid E, Soibinet P, Perol D, Chabaud S, Italiano A, Cesne AL. Discontinuation versus continuation of imatinib in patients with advanced gastrointestinal stromal tumours (BFR14): exploratory long-term follow-up of an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2024 Sep;25(9):1163-1175. doi: 10.1016/S1470-2045(24)00318-8. Epub 2024 Aug 7.

    PMID: 39127063DERIVED

  • Patrikidou A, Domont J, Chabaud S, Ray-Coquard I, Coindre JM, Bui-Nguyen B, Adenis A, Rios M, Bertucci F, Duffaud F, Chevreau C, Cupissol D, Perol D, Emile JF, Blay JY, Le Cesne A; French Sarcoma Group. Long-term outcome of molecular subgroups of GIST patients treated with standard-dose imatinib in the BFR14 trial of the French Sarcoma Group. Eur J Cancer. 2016 Jan;52:173-80. doi: 10.1016/j.ejca.2015.10.069. Epub 2015 Dec 11.

    PMID: 26687836DERIVED

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2006

First Posted

August 23, 2006

Study Start

May 1, 2002

Primary Completion

April 1, 2012

Study Completion

May 1, 2013

Last Updated

February 24, 2014

Record last verified: 2014-02

Locations

FR(8)