Study of Dose Escalation Versus no Dose Escalation of Imatinib in Metastatic Gastrointestinal Stromal Tumors (GIST) Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine if escalating the dose of imatinib to keep the drug blood level at ≥ 1100 ng/ml leads to better outcomes for patients.

Official Title
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A Randomized, Phase 3 Study of Dose Escalation Versus No Dose Escalation of Imatinib In Metastatic GIST Patients With Imatinib Trough Levels Less Than 1100 Nanograms/mL

Conditions
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Gastrointestinal Stromal Tumors

Intervention / Treatment
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* Drug: Imatinib mesylate
* Drug: Imatinib mesylate
* Drug: Imatinib mesylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Unresectable and/or metastatic GIST Currently receiving imatinib 400 mg per day for a minimum of 4 weeks prior to registration, and for no more than 6 months prior to registration. This must be the first time that the patient has been treated for metastatic and/or unresectable GIST For patients who received imatinib following surgery at the time of an initial diagnosis of GIST, there must be a 6 month interval between completion of imatinib and the diagnosis of metastatic GIST Good physical functioning (ECOG Performance Status of 0 or 1) Generally, good function of organ such as liver and kidneys Exclusion Criteria: Disease progression during adjuvant therapy with imatinib (adjuvant treatment is treatment that is given after surgery for GIST) Known intolerance of imatinib at a dose of 400 mg/day or higher Prior systemic therapy for advanced GIST with imatinib or those who have been on imatinib for longer than 6 months for unresectable and/or metastatic disease Major surgery within 2 weeks prior to Day 1 of study or who have not yet recovered from prior surgery Use of coumadin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon) Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation < 2 weeks or who have not recovered from side effects of this therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Patients with blood level less than 1100 will continue imatinib 400 mg daily | Drug: Imatinib mesylate<br>* 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops<br>* Other names: Glivec;|
| Active Comparator: Arm B<br>Patients with blood level less than 1100 dose adjust imatinib mesylate to goal blood level ≥1100 ng/mL | Drug: Imatinib mesylate<br>* 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops<br>* Other names: Glivec;|
| Active Comparator: Arm C<br>Patients with blood level ≥1100 will continue imatinib 400 mg daily | Drug: Imatinib mesylate<br>* 400 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops<br>* Other names: Glivec;|
| Active Comparator: Arm D<br>Patients with tumors that harbor exon 9 mutations will continue imatinib mesylate at 400 mg or dose escalate up to 800 mg daily | Drug: Imatinib mesylate<br>* 400, 600 or 800 mg daily. Number of cycles: until disease progression or unacceptable toxicity develops<br>* Other names: Glivec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Lesions for Progression or Response Via RECIST Criteria |  | Every 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GIST, Gastrointestinal stromal tumors, Exon 9, Gleevec, Imatinib blood levels