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

NCT02260505 | Completed Phase 3 DMC

• 2 other identifiers: IMADGIST2013-001372-37
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 17

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 will continue Imatinib treatment for 3 more years, allowing to determine if the continuation of this treatment is efficient for disease control, in terms of Disease Free Survival improvement. In the second arm, patients will discontinue the Imatinib treatment, as standard practice. This arm will allow to determine if the re-introduction of Imatinib at relapse is still an efficient treatment for the control of disease.

Conditions

Gastrointestinal Stromal Tumors; Resected Gastrointestinal Stromal Tumors; Non-metastatic; High Risk of Recurrence; KIT Gene Mutation

Keywords

Gastrointestinal Stromal Tumors; Non-metastatic; KIT +; Imatinib; Adjuvant treatment; High risk of recurrence; Tyrosine kinase inhibitor; Disease Free Survival; Overall survival; Time To Secondary Resistance; Safety profile; Quality of Life during treatment

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival (DFS)

  Time from the date of randomisation to the first documented relapse or death due to any cause. Patients with no event at the time of analysis will be censored at the date of the last adequate tumour assessment. The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

  6 years (i.e. at the the time of last patient last visit)

Secondary Outcomes (5)

• Overall Survival (OS)

  6 years (i.e. at the the time of last patient last visit)

• Time to Secondary Resistance (TSR)

  6 years (i.e. at the the time of last patient last visit)

• Percentage of patients in Complete Response (%CR) in interruption arm after reintroduction of Imatinib

  6 years (i.e. at the the time of last patient last visit)

• Frequency of Adverse Events (AE)

  6 years (i.e. at the the time of last patient last visit)

• Patient's Quality of Life (QoL)

  6 years (i.e at the the time of last patient last visit)

Study Arms (2)

Imatinib maintenance

EXPERIMENTAL

Maintenance of Imatinib at the last dose routinely taken by the patient in the 3 years period prior to randomization (either 300 or 400 mg/day). Increase dose up to 800 mg/day if relapse according to RECIST 1.1 criteria. Any relapse/progressive disease at 800 mg/day will lead to Imatinib permanent discontinuation and study discontinuation. In case of toxicity, Imatinib dose will be interrupted or adjusted in accordance with Imatinib Specific Product Characteristics (SPC).

Drug: Imatinib maintenance

Imatinib Interruption

NO INTERVENTION

Treatment corresponding to standard practice : interruption of Imatinib from the day of randomization. Reintroduction of Imatinib at 400 mg/day after first relapse according to RECIST 1.1 criteria; Then increase dose to 800 mg/day after 2d relapse. Any relapse/progressive disease at 800 mg/day will lead to Imatinib permanent discontinuation and study discontinuation. In case of toxicity, Imatinib dose will be interrupted or adjusted in accordance with Imatinib SPC.

Interventions

Imatinib maintenance DRUG

Either 300 or 400 mg/day in accordance with the last dose routinely taken by the patient in the 3-year period before randomization. The treatment will be orally taken at time of meal with a large glass of water

Also known as: Glivec, Imatinib mésilate

Imatinib maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• \) Serum creatinine ≤ 1.5 x ULN or
• \) 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (17)

Institut Paoli-Calmettes

Marseille, Bouches Du Rhône, 13273, France

Location

Centre Hospitalier Universitaire La Timone

Marseille, Bouches Du Rhône, 13386, France

Location

Centre Georges François Leclerc

Dijon, Côte d'Or, 21079, France

Location

CHRU de Besançon - Hôpital Minjoz

Besançon, Doubs, 25030, France

Location

Institut Bergonié

Bordeaux, Gironde, 33076, France

Location

Centre Régional de Lutte contre le Cancer de Montpellier

Montpellier, Hérault, 34298, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, Loire Atlantique, 44805, France

Location

Centre Hospitalier universitaire Robert Debré

Reims, Marne, 51092, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54519, France

Location

Centre Oscar Lambret

Lille, Nord, 59020, France

Location

Institut de cancérologie LUCIEN NEUWIRTH

Saint-priest-en-jarez, Pays de la Loire Region, 42270, France

Location

Centre Léon Bérard

Lyon, Rhône, 69008, France

Location

Institut de Cancérologie Gustave Roussy

Villejuif, Val De Marne, 94805, France

Location

AP-HP Hôpital Saint-Antoine

Paris, 75571, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

CHRU Strasbourg - Hôpital Hautepierre

Strasbourg, 67098, France

Location

AP-HP Hôpital Européen Georges Pompidou

Paris, Île-de-France Region, 75908, France

Location

Related Publications (30)

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MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Jean-Yves Blay, Pr

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: October 9, 2014
• Study Start: December 24, 2014
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Locations

FR (17)