Dasatinib in Treating Patients With Stage III Melanoma That Cannot Be Removed By Surgery or Stage IV Melanoma

Study Overview
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Brief Summary
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This phase II trial is studying how well dasatinib works in treating patients with stage III melanoma that cannot be removed by surgery or stage IV melanoma. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with stage III unresectable or stage IV melanoma treated with dasatinib. II. Determine the progression-free survival of patients treated with this drug. SECONDARY OBJECTIVES: I. To assess the expression of targets of Dasatinib prior to treatment by obtaining pre-treatment biopsies or examining paraffin-embedded tissues from previous tumor resections. II. In selected patients (approximately 5-10) where tumor tissue is available pre-treatment and can be obtained post-treatment with Dasatinib (21 days after initiation of therapy), to determine if Dasatinib induces changes in expression of selected targets and downstream mediators, including MEK, ERK and RSK-1. III. To assess toxicity. OUTLINE: Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks.

Official Title
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A Phase 2 Study of Dasatinib in Advanced Melanoma

Conditions
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Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma

Intervention / Treatment
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* Drug: dasatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed stage III unresectable or stage IV melanoma Measurable disease Must have evidence of tumor growth or new lesions within the past 6 months No large pleural effusions No known brain metastases or leptomeningeal metastases Previously treated brain metastases allowed provided there is no requirement for steroids AND no evidence of progression for ≥ 8 weeks after treatment ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100% Life expectancy > 3 months WBC ≥ 3,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL (transfusions allowed) Bilirubin ≤ 1.5 mg/mL AST and ALT ≤ 2.5 times upper limit of normal (ULN) PT/INR and PTT normal Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min No medical condition that may affect the ability to swallow and retain dasatinib tablets, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication Requirement for IV alimentation Prior surgical procedures affecting absorption Active peptic ulcer disease No clinically significant cardiovascular disease, including any of the following: Myocardial infarction or ventricular tachyarrhythmia within the past 6 months Prolonged QTc > 480 msec Major conduction abnormality (unless a cardiac pacemaker is present) No uncontrolled intercurrent illness including, but not limited to, any of the following: Ongoing or active infection History of significant congenital or acquired bleeding disorder, including any of the following: Von Willebrand's disease Antifactor VIII antibodies Dyspnea at rest or with minimal exertion Uncontrolled seizure disorder Psychiatric illness or social situations that would preclude study compliance Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other active malignancy within the past 3 years except curatively treated stage I malignancies or resected skin carcinomas Recovered from prior therapy Prior adjuvant therapy for stage II or III melanoma allowed No prior cytotoxic therapy for metastatic melanoma No prior dasatinib or other inhibitors of src, bcr-abl, c-Kit, EPHA2, and PDGFRβ No more than 2 prior immunomodulator therapies for metastatic melanoma At least 1 week since prior and no concurrent warfarin or other anticoagulants or medications that inhibit platelet function (including acetylsalicylic acid) At least 1 week since prior and no concurrent steroids or other immunosuppressive agents Concurrent steroids to treat induced pleural effusions allowed At least 3 weeks since prior immunomodulators including, but not limited to, any of the following: Aldesleukin Cancer vaccines T-cell-activating monoclonal antibodies At least 4 weeks since prior radiotherapy Prior palliative radiotherapy to a single site of disease allowed (tumor is not considered evaluable for response unless there is tumor progression at the site of radiation) More than 7 days since prior and no concurrent CYP3A4 inhibitors At least 7 days since prior and no concurrent agents with proarrhythmic potential No other concurrent investigational agents No other concurrent anticancer agents or therapies No concurrent enzyme-inducing anticonvulsant agents No concurrent grapefruit or grapefruit juice No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent CYP3A4 inducers

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: Treatment (kinase inhibitor therapy)<br>Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: dasatinib<br> <br> * Other names: Sprycel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Objective Response(Partial Response and Complete Response) as Measured by RECIST Criteria | Only those patients who have measurable disease present at baseline, have received at least one course of therapy, and have had their disease re-evaluated will be considered evaluable for response. A Simon's optimum two-stage design will be used. | After every 8 weeks (or 2 courses), assessed up to 4 weeks after completion of treatment | 
| Progression-free Survival | Progression will be evaluated in this study using the new international criteria proposed by the RECIST Committee. A Simon's optimum two-stage design will be used | Time from start treatment to time of progression, assessed up to 6 months |