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

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