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Gastrointestinal Stromal TumorsPhase 3ImadGistNCT02260505

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

A Phase 3 study testing Imatinib maintenance in people with Gastrointestinal Stromal Tumors and Resected Gastrointestinal Stromal Tumors, run by Centre Leon Berard at 17 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Imatinib maintenance
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
17 sitesFrance
Study dates
24 Dec 2014to Dec 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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.

Who cannot join

  • 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.
Show all 10Show fewer
  • 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

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

France17 sites

  • CHRU de Besançon - Hôpital Minjoz

    Besançon, Doubs, 25030

  • Institut Bergonié

    Bordeaux, Gironde, 33076

  • Centre Georges François Leclerc

    Dijon, Côte d'Or, 21079

  • Centre Oscar Lambret

    Lille, Nord, 59020

  • Centre Léon Bérard

    Lyon, Rhône, 69008

  • Institut Paoli-Calmettes

    Marseille, Bouches Du Rhône, 13273

  • Centre Hospitalier Universitaire La Timone

    Marseille, Bouches Du Rhône, 13386

  • Centre Régional de Lutte contre le Cancer de Montpellier

    Montpellier, Hérault, 34298

  • AP-HP Hôpital Saint-Antoine

    Paris, 75571

  • AP-HP Hôpital Européen Georges Pompidou

    Paris, Île-de-France Region, 75908

  • Centre Hospitalier universitaire Robert Debré

    Reims, Marne, 51092

  • Centre Eugène Marquis

    Rennes, 35042

  • Institut de Cancérologie de l'Ouest

    Saint-Herblain, Loire Atlantique, 44805

  • Institut de cancérologie LUCIEN NEUWIRTH

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

  • CHRU Strasbourg - Hôpital Hautepierre

    Strasbourg, 67098

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54519

  • Institut de Cancérologie Gustave Roussy

    Villejuif, Val De Marne, 94805

Other trials in France

About this study

Official title: A Randomized Multicenter Phase III Trial Evaluating the Interest of Imatinib Treatment Maintenance or Interruption After 3 Years of Adjuvant Treatment in Patients With Gastrointestinal Stromal Tumours (GIST)

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.

Read the 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 approximately 12 cases per million people, corresponding to approximately 800 new cases per year in France.

A large majority of GISTs harbour activating mutations in the proto-oncogenes KIT and/or PDGFRA, both coding cell-surface cytokine receptors with tyrosine-protein kinase activity.

Imatinib mesilate (Glivec®, Novartis Pharma SAS) is a selective tyrosine kinase inhibitor, leading to inhibition of KIT and PDGFRA signalling pathways. The introduction of imatinib has revolutionised the therapeutic management of GIST patients and has provided an unprecedented demonstration of the clinical benefit of a targeted therapy for patients with advanced/metastatic solid tumors. First results from prospective trials conducted with imatinib in GIST patients have demonstrated a 300% increase in median overall survival, and a likely 100% increase in 5 and 10-year survival as compared to cytotoxic chemotherapy.

The successful use of imatinib in the treatment of advanced GISTs and the significant risk of recurrence of advanced GISTs have prompted the investigation of the clinical benefit of imatinib as a post-operative adjuvant therapy. Two prospective randomized Phase III trials have demonstrated that adjuvant imatinib treatment significantly prolong overall survival (OS) and recurrence-free survival (RFS) when given for 3 years. To date, imatinib is also indicated in the adjuvant setting after complete resection of primary, localized, KIT-positive GIST at high risk of recurrence. However, the optimal treatment duration remains unclear and it should be determined whether

  1. prolonged use of adjuvant imatinib beyond 3 years may enable to reduce the risk of GIST recurrence and to improve overall survival, and
  2. imatinib rechallenge is efficient for treating recurrence after completion of 3-year adjuvant imatinib therapy.

This trial is an open-label, randomized, multicenter phase III study aiming to determine the clinical impact of maintaining imatinib treatment beyond 3 years in the adjuvant setting for patients with resected GISTs at high risk of recurrence according to the National Comprehensive Cancer Network Task Force on GIST (NCCN) risk classification.

Being tested
Imatinib maintenance
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
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Imatinib maintenanceDrug

    Also called Glivec, Imatinib mésilate

    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

Study groups in NCT02260505
Study groupRoleWhat they receive
Imatinib maintenanceExperimentalMaintenance 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).
Receives: Drug: Imatinib maintenance
Imatinib InterruptionNo interventionTreatment 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (5)

  1. Overall Survival (OS)

    Time from the date of randomization until the date of death due to any cause and censored at the date of last contact for patients alive at last contact. The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

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

  2. Time to Secondary Resistance (TSR)

    Time from the date of randomization until the date of first relapse under Imatinib treatment (i.e first relapse in the "Imatinib maintenance arm" and relapse after reintroduction of Imatinib in the "Interruption of Imatinib arm"). The results will be analyzed according to the study arm and randomization strata to wich patients were assigned.

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

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

    Percentage of patients in Complete Response (CR) after reintroduction of Imatinib treatment for patients assigned to the interruption arm and who experience GIST recurrence. CR is assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

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

  4. Frequency of Adverse Events (AE)

    The assessment of safety will be based mainly on the frequency of AE based on the Common Toxicity Criteria version 4 grade. AE will be coded according to the Medical Dictionary for Regulatory Activities (MedDRA). Descriptive statistics will be provided for characterizing and assessing patient tolerance to treatment. Patients with at least either one serious AE, or one grade 3-4, or one AE requiring the interruption of study treatment, will be described by study arm and compared using a Pearson's Chi2 test or a Fisher's exact test, if adequate. Patients will be analyzed according the duration of exposure to imatinib

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

  5. Patient's Quality of Life (QoL)

    QoL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire (QLQ-C30). Descriptive statistics (e.g. means and medians) will be used to summarize the scored scales at it scheduled assessment time point of the questionnaire. The distribution of time to definitive health-related QoL deterioration by study arms will be estimated using the Kaplan-Meier method. The time to definitive deterioration is defined as the time from the date of randomization to the date of event, wich is defined as > 10 points decrease from baseline of QLQ-C30 global score (items 29 and 30) or death due to any cause. If patient has not had an event, time to QoL deterioration will be censored at the date of last adequate evaluation.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2014 (estimated)
  2. Study start24 Dec 2014
  3. Primary completionDec 2023
  4. Study completionDec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02260505
Sponsor's protocol ID
IMADGIST
Other IDs
2013-001372-37
Acronym
ImadGist
Status last verified
Jan 2024
First submitted
30 Jul 2014
Last updated
5 Jan 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Blackstein ME, Blay JY, Corless C, Driman DK, Riddell R, Soulieres D, Swallow CJ, Verma S; Canadian Advisory Committee on GIST. Gastrointestinal stromal tumours: consensus statement on diagnosis and treatment. Can J Gastroenterol. 2006 Mar;20(3):157-63. doi: 10.1155/2006/434761.

    PubMed 16550259

  • Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, Corless CL, Fletcher CD, Roberts PJ, Heinz D, Wehre E, Nikolova Z, Joensuu H. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol. 2008 Feb 1;26(4):620-5. doi: 10.1200/JCO.2007.13.4403.

    PubMed 18235121

  • Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, Tanaka M, Hecht JR, Heinrich MC, Fletcher CD, Crowley JJ, Borden EC. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. 2008 Feb 1;26(4):626-32. doi: 10.1200/JCO.2007.13.4452.

    PubMed 18235122

  • Blay JY, von Mehren M, Blackstein ME. Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors. Cancer. 2010 Nov 15;116(22):5126-37. doi: 10.1002/cncr.25267.

    PubMed 20661913

  • 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.

    PubMed 17369574

  • Casali PG, Jost L, Reichardt P, Schlemmer M, Blay JY; ESMO Guidelines Working Group. Gastrointestinal stromal tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008 May;19 Suppl 2:ii35-8. doi: 10.1093/annonc/mdn080. No abstract available.

    PubMed 18456761

  • ClinicalTrials.gov. Imatinib mesilate or observation only in treating patients who have undergone surgery for localized gastrointestinal stromal tumor. NCT identifier: NCT00103168. 13-12-2009. Ref Type: Online Source

  • ClinicalTrials.gov. Five year adjuvant imatinib mesilate (Gleevec®) in gastrointestinal stromal tumor (GIST). NCT Identifier: NCT00867113. 24-8-2011. Ref Type: Online Source

  • Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol. 2008;3:557-86. doi: 10.1146/annurev.pathmechdis.3.121806.151538.

    PubMed 18039140

  • Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer. 2011 Nov 17;11(12):865-78. doi: 10.1038/nrc3143.

    PubMed 22089421

  • Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Mar 28;373(9669):1097-104. doi: 10.1016/S0140-6736(09)60500-6. Epub 2009 Mar 18.

    PubMed 19303137

  • DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000 Jan;231(1):51-8. doi: 10.1097/00000658-200001000-00008.

    PubMed 10636102

  • Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol. 2002 May;33(5):466-77. doi: 10.1053/hupa.2002.124122.

    PubMed 12094371

  • Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002 Aug 15;347(7):472-80. doi: 10.1056/NEJMoa020461.

    PubMed 12181401

  • Demetri GD, von Mehren M, Antonescu CR, DeMatteo RP, Ganjoo KN, Maki RG, Pisters PW, Raut CP, Riedel RF, Schuetze S, Sundar HM, Trent JC, Wayne JD. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw. 2010 Apr;8 Suppl 2(0 2):S1-41; quiz S42-4. doi: 10.6004/jnccn.2010.0116.

    PubMed 20457867

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Imatinib maintenance in people with Gastrointestinal Stromal Tumors and Resected Gastrointestinal Stromal Tumors, run by Centre Leon Berard at 17 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Free Survival (DFS) (time frame: 6 years (i.e. at the the time of last patient last visit)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02260505, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.

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