Dasatinib as First-Line Therapy in Treating Patients With Gastrointestinal Stromal Tumors

Study Overview
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Brief Summary
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RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well dasatinib works as first-line therapy in treating patients with gastrointestinal stromal tumors.

Detailed Description
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OBJECTIVES: Primary To determine the efficacy of dasatinib as assessed by fusion PET/CT scan in patients with gastrointestinal stromal tumors. Secondary To determine the efficacy and safety of dasatinib in these patients. To correlate the efficacy of dasatinib with KIT and PDGFR mutational status. To correlate the efficacy and safety of dasatinib with dasatinib drug exposure. To determine the efficacy of second-line treatment with another TK-inhibitor. OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days for 26 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Official Title
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Dasatinib First-Line Treatment in Gastrointestinal Stromal Tumors. A Multi Center Phase II Trial

Conditions
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Gastrointestinal Stromal Tumor

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed gastrointestinal stromal tumor (GIST) Measurable disease by conventional scans (CT scan or MRI) within 2 weeks prior to study registration Positive PET/CT scan with [^18F]-fluorodeoxyglucose uptake of the target lesions within 2 weeks prior to study registration No signs or history of CNS metastases PATIENT CHARACTERISTICS: WHO performance status 0-2 Hemoglobin ≥ 90 g/L (transfusion allowed) Neutrophil count ≥ 1.5 x 10^9/L Platelet count ≥ 100 x 10^9/L Bilirubin ≤ 2 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN AST and/or ALT ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 12 months after completion of study therapy No other malignancy within the past 5 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer No hypocalcemia (i.e., serum calcium ≤ lower limit of normal) No clinically significant cardiovascular disease, including any of the following: Uncontrolled hypertension Congestive heart failure within the past 6 months QTc > 450 msec or major conduction abnormality (unless a cardiac pacemaker is present) No concurrent medical condition (e.g., active autoimmune disease or uncontrolled diabetes) that would impair the ability of the patient to participate in the study (at the judgment of the investigator) or that may increase the risk of toxicity, including any of the following: Pleural or pericardial effusion of any grade Clinically significant coagulation or platelet function disorder (e.g., known von Willebrand's disease) Infection requiring intravenous antibiotics Ongoing significant gastrointestinal bleeding Nausea, vomiting, or malabsorption syndrome that could interfere with ingestion or absorption of oral dasatinib No known hypersensitivity to study drug PRIOR CONCURRENT THERAPY: No prior therapy for GIST, particularly tyrosine kinase inhibitors at any time More than 30 days since prior participation in a clinical trial At least 7 days since prior and no concurrent potent CYP3A4 inhibitors, including any of the following: Itraconazole, ketoconazole, miconazole, and voriconazole Amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, and ritonavir Ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib mesylate, isoniazid, ketamine, nefazodone, nicardipine, propofol, quinidine, and telithromycin At least 7 days since prior and no concurrent medications known to prolong the QT interval, including any of the following: Quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, and dofetilide Erythromycin and clarithromycin Chlorpromazine, haloperidol, mesoridazine, thioridazine, and pimozide Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, and lidoflazine No concurrent IV bisphosphonates during the first 8 weeks of study treatment No other concurrent experimental drugs or anticancer therapy No concurrent drugs contraindicated for use with dasatinib, according to the dasatinib investigator's brochure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Dasatinib<br> | Drug: dasatinib<br>* Dasatinib is given orally 70 mg BID. Dasatinib will be continued until progression, unacceptable toxicity and up to 2 years (26 cycles, each cycle lasting 4 weeks).<br>* Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as assessed by fusion PET/CT scan according to EORTC PET Study Group criteria |  | at 4 weeks compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response as assessed by CT scan/MRI |  | according to RECIST criteria | 
| Best response as assessed by fusion PET/CT scan |  | at 4 weeks | 
| Clinical benefit |  | Clinical benefit is defined as CR, PR, or as SD lasting at least 12 weeks, determined according to RECIST | 
| Time to progression |  | calculated from registration until progression or death due to tumor | 
| Progression-free survival |  | calculated from registration until progression or death | 
| Time to treatment failure |  | calculated from registration until premature trial treatment termination due to any reason | 
| Overall survival |  | Overall survival will be calculated from registration until death or last follow-up, up to 5 years. | 
| Adverse drug reactions according to NCI CTCAE v3.0 |  | Tolerability will be assessed based on the frequency and severity of Adverse Drug Reactions (ADR) coded according to NCI CTCAE v3.0. | 

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