Status:

COMPLETED

Efficiency of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)

Lead Sponsor:

Centre Leon Berard

Conditions:

Gastrointestinal Stromal Tumors

Resected Gastrointestinal Stromal Tumors

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

This is a 2 arms study concerning patients with primary GIST who followed an Imatinib adjuvant treatment for 3 years after surgery and who have a high risk of recurrence. In the first arm, patients w...

Detailed Description

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms, mostly diagnosed between 55 and 60 years of age, which account for 5% of all sarcomas. Worldwide annual incidence is approximat...

Eligibility Criteria

Inclusion

  • Age ≥ 18 years at the day of consenting to the study
  • Patients must have histologically confirmed diagnosis of localized GIST with documented KIT (CD117) positivity (by polyclonal DAKO antibody staining)
  • Documented macroscopically complete surgical R0 or R1 resection of primary GIST lesion with no evidence of residual lesions or metastases on the baseline CT-scan or MRI performed no more than 4 weeks before randomization.
  • Risk of tumor recurrence ≥ 35% according to National Comprehensive Cancer Network Task Force on GIST (NCCN) risk classification (Demetri et al., 2010) (See Appendix 1)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  • Patients must be under imatinib treatment (at 300 or 400 mg/day) initiated immediately after resection and maintained for 3 years (i.e. 36 months ± 3 months at the time of randomization) with no more than 3 consecutive months or 6 months in total of interruption during these past 3 years.
  • Patients must have normal organ and bone marrow function at baseline as defined below:
  • absolute neutrophil count (ANC) ≥ 1.5 G/L, platelet count ≥ 100 G/L, and haemoglobin of ≥ 9 g/dL).
  • Serum total bilirubin ≤ 1.5 (upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (or 5 x ULN in case of hepatic metastases at time of reintroduction)
  • Adequate renal function assessed by at least one of the following:
  • 1\) Serum creatinine ≤ 1.5 x ULN or
  • 2\) creatinine clearance estimate ≥ 50 mL/min (as calculated according to Cockcroft-Gault formula or MDRD formula for patients \> 65 years).
  • Recovered from prior anti-neoplasia treatment-related toxicity (persistent treatment-related toxicity \< Grade 2 as per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 are accepted)
  • Women of childbearing potential are required to have a negative serum pregnancy test within 72 hours prior to randomization. A positive urine test must be confirmed by a serum pregnancy test
  • Patient must use effective contraception at least 4 weeks prior to study entry, during the study participation and for at least 30 days post-treatment (not applicable for women of non-childbearing potential)
  • Ability to understand and willingness for follow-up visits.
  • Covered by a medical insurance.
  • Signed and dated informed consent document indicating that the patient has been informed of all aspects of the trial prior to enrolment.

Exclusion

  • Pregnant or breastfeeding women
  • Patient concurrently using other approved or investigational antineoplastic agents
  • Any contra-indication to imatinib treatment as per Glivec® SPC
  • Patient with GIST harboring the mutation D842V in PDGFRA
  • Major concurrent disease affecting cardiovascular system, liver, kidneys, haematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures or results.
  • Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) unless the patient has been free of the disease for at least 3 years.
  • Patient receiving concurrent treatment with warfarin (acceptable alternative: low-molecular weight heparin) or any prohibited concomitant and/or concurrent medications
  • 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)
  • Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  • Major surgery within 2 weeks prior to study entry

Key Trial Info

Start Date :

December 24 2014

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

December 1 2023

Estimated Enrollment :

136 Patients enrolled

Trial Details

Trial ID

NCT02260505

Start Date

December 24 2014

End Date

December 1 2023

Last Update

January 5 2024

Active Locations (17)

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Page 1 of 5 (17 locations)

1

Institut Paoli-Calmettes

Marseille, Bouches Du Rhône, France, 13273

2

Centre Hospitalier Universitaire La Timone

Marseille, Bouches Du Rhône, France, 13386

3

Centre Georges François Leclerc

Dijon, Côte d'Or, France, 21079

4

CHRU de Besançon - Hôpital Minjoz

Besançon, Doubs, France, 25030