Dasatinib in Treating Patients With Locally Advanced or Metastatic Mucosal Melanoma, Acral Melanoma, or Vulvovaginal Melanoma That Cannot Be Removed By Surgery

Inclusion Criteria for Pre-Registration (Step 0):

* Histologically or cytologically confirmed melanoma of 1 of the following subtypes:

  * Acral melanoma (defined as occurring on the palms, soles, or subungual sites)
  * Melanoma arising from the vagina and/or vulva
  * Melanoma arising on other mucosal surface (not vagina or vulva)
* Unresectable locally advanced or metastatic disease
* c-KIT mutation identified by polymerase chain reaction (PCR) and sequencing meeting 1 of the following criteria:

  * At least 1 mutation in exon 9, 11, 13, 17, or 18
  * At least 1 mutation in an exon not listed above and approved by central reviewer
* Metastatic tumor blocks are required for the evaluation of KIT mutations or amplifications
* Prior radiotherapy to a measurable lesion allowed provided there is radiographic evidence of progression of that lesion
* No other concurrent malignancies except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or other malignancies from which the patient has been continuously disease-free for ≥ 5 years
* ECOG performance status 0-1

Exclusion Criteria for Pre-Registration (Step 0):

* Prior treatment with targeted therapies directed to c-KIT/PDGFR (e.g., imatinib or sunitinib)
* Ocular melanoma
* Evidence of bleeding diathesis
* Clinically significant psychiatric illness or social situations that would limit compliance with study requirements
* Clinically significant cardiovascular disease including the following:

  * Myocardial infarction or ventricular tachyarrhythmia within 6 months
  * Prolonged QTc \>480 msec (Fridericia correction)
  * Ejection fraction less than institutional normal
  * Major conduction abnormality (unless a cardiac pacemaker is present)
  * Patients with any cardiopulmonary symptoms of unknown cause (e.g., shortness of breath, chest pain, etc.) are to be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation
  * Patients with underlying cardiopulmonary dysfunction are excluded from the study

Inclusion Criteria for Registration (Step 1):

* Meeting the eligibility criteria for pre-registration (Step 0)
* The melanoma must harbor a c-KIT mutation determined by PCR and sequencing as defined in the protocol either by local assessment or Massachusetts General Hospital (MGH)
* Measurable disease, defined as at least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* At least 4 weeks since prior chemotherapy, radiotherapy or immunotherapy and the beginning of protocol therapy and the patient must have recovered from toxicity due to the previous therapy
* History or clinical evidence of brain metastasis allowed provided the following criteria are met:

  * Completed radiotherapy or surgical treatment of brain lesions and there is no evidence of central nervous system (CNS) progression for ≥ 8 weeks
  * Must not require corticosteroids for treatment of cerebral edema from brain metastases
* Negative pregnancy test
* Fertile patients must use effective contraception
* Patients must have the following within 4 weeks of registration:

  * computed tomography (CT) chest with intravenous (IV) and oral agent
  * CT pelvis/abdomen with IV and oral agent
  * MRI brain with gadolinium
* Baseline bone scan required for patients with known bone metastases, elevated alkaline phosphatase, or symptoms raising suspicion of bone metastases
* White blood count (WBC) ≥ 3,000/mm³
* Absolute granulocyte count (AGC) ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 2.0 times upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min
* Total bilirubin ≤ 1.5 times ULN (\< 3.0 times ULN in the presence of Gilbert disease)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases)
* Serum potassium and magnesium normal (repletion allowed)
* Total serum calcium or ionized calcium ≥ institutional lower limit of normal
* International normalized ratio (INR) ≤ 1.5 and partial thromboplastin time (PTT) wtihin normal limits

  * Therapeutic anticoagulation with warfarin allowed provided INR ≤ 1.5 or PTT normal prior to initiating anticoagulation therapy

Exclusion Criteria for Registration (Step 1):

* Pregnant or nursing
* Concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (i.e., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John wort)
* Uncontrolled hypertension, defined as systolic blood pressure ≥ 150 mm Hg or diastolic blood pressure ≥ 90 mm Hg

  * Hypertension that is adequately controlled with medication allowed
* QTc prolongation, defined as a QTc interval ≥ 450 msecs
* Serious intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics