Imatinib Mesylate and Sunitinib in Treating Patients With Gastrointestinal Stromal Tumors

Study Overview
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Brief Summary
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RATIONALE: Imatinib mesylate and sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate given together with sunitinib in treating patients with gastrointestinal stromal tumors.

Detailed Description
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OBJECTIVES: To determine the maximum tolerated dose of imatinib mesylate in combination with sunitinib malate in patients with gastrointestinal stromal tumors. To determine the toxicity of this regimen in these patients. To determine the antitumor activity in patients treated with this regimen. OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients receive oral sunitinib malate once daily on days 1-14 in course 1 and on days 1-42 in all subsequent courses. Beginning in course 2, patients also receive oral imatinib mesylate once or twice daily on days 1-42. Courses repeat every 6 weeks in the absence of unacceptable toxicity. Blood samples are collected on day 15 and day 43 for pharmacokinetics. After completion of study treatment, patients are followed every 6 months.

Official Title
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A Phase I Study of Imatinib Mesylate and SU011248 for Patients With Gastrointestinal Stromal Tumors

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: imatinib mesylate
* Drug: sunitinib malate
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Biopsy proven gastrointestinal stromal tumor Patients previously treated with imatinib mesylate must have documented progression of disease Untreated disease allowed Must have ≥ 1 measurable lesion by RECIST No history of or known brain metastases, spinal cord compression,carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan PATIENT CHARACTERISTICS: ECOG performance status 0-2 ANC ≥ 1,500/μL Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 150,000/μL Total serum bilirubin ≤ 2.0 mg/dL Serum calcium ≤ 12.0 mg/dL Serum creatinine ≤ 1.8 mg/dL AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy) Able to take oral medications Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No grade 3 hemorrhage within the past 4 weeks No myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism within the past 6 months No ongoing cardiac dysrhythmias ≥ grade 2 No prolonged QTc interval on baseline EKG No hypertension that cannot be controlled by medications (BP > 150/100 mm Hg, despite medical therapy) No pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication No known HIV or AIDS-related illness or other active infection No other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator, preclude study entry No malabsorption syndrome No prior intolerance of imatinib mesylate or toxicity necessitating dose modification No prior intolerance of sunitinib malate or toxicity necessitating dose modification PRIOR CONCURRENT THERAPY: Recovered from all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedures No major surgery or radiotherapy within the past 4 weeks No concurrent treatment on another clinical trial, except supportive care trials or non-treatment trials (e.g., quality of life) No concurrent ketoconazole and other agents known to induce CYP3A4 No concurrent theophylline or phenobarbital and/or other agents metabolized by the cytochrome P450 system No ongoing therapeutic doses of coumadin, except low-dose oral coumadin up to 2 mg once daily for thrombosis prophylaxis No concurrent Hypericum perforatum (St. John's wort) or other herbal medications

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic Intervention<br> | Drug: imatinib mesylate<br>* will start at 200 mg daily and will be escalated up to 400 mg bid.If the 400 mg bid dose is tolerated, no further dose escalation will be performed. In the case of excessive toxicity on the starting dose, the option for de-escalation is provided. Sunitinib will start at 25 mg daily and if tolerated, will be escalated to 37.5 mg daily for subsequent dose levels.<br>* Other names: None noted;Drug: sunitinib malate<br> <br> * Other names: none noted;Other: pharmacological study<br> <br> * Other names: Not noted;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of imatinib mesylate in combination with sunitinib malate |  | at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile as assessed by NCI CTCAE v3.0 |  | every 6 weeks | 
| Pharmacokinetics |  | days 15 & 43 | 
| Preliminary data on anti-tumor activity of these drugs as assessed by RECIST |  | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gastrointestinal stromal tumor