Imatinib Mesylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

Inclusion Criteria:

* Histologically or cytologically confirmed inoperable stage III or IV melanoma that began on acral skin or mucosa

  * Patients with cutaneous melanoma that began on sun exposed sites of the skin and whose pathology demonstrates signs of sun damage (solar elastosis) involving the skin surrounding their primary melanoma are eligible
* Must have sufficient tumor tissue available for FISH and DNA sequencing

  * Patients must have either a true amplification of 4q12 or a detectable mutation of c-KIT
  * If no banked tumor tissue is available, or if the available banked tumor tissue is insufficient for the necessary testing, then a repeat biopsy procedure will be required to collect the necessary tumor sample
* Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria
* No known untreated brain or epidural metastases

  * Brain metastases that have been treated and deemed stable are allowed
* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* Life expectancy greater than 3 months
* WBC ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)

  * Patients with unexplained hyperbilirubinemia that is clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert's syndrome) may be eligible
* AST and ALT ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present)
* Creatinine ≤ 1.5 times ULN
* PT and PTT ≤ 1.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception before and during study participation
* No history of allergic reactions attributed to compounds of similar chemical or biological composition to imatinib mesylate
* No concurrent uncontrolled illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable anginapectoris
  * Cardiac arrhythmia resulting in hemodynamic instability
  * Intestinal malabsorption disorders
  * Psychiatric illness or social situations that would limit study compliance
* Recovered to grade 1 from all prior therapies with the exception of alopecia
* At least 2 weeks since prior radiotherapy (≤ 3,000 cGy to fields including substantial marrow)
* At least 2 weeks since prior isolated limb infusion or perfusion (must have evidence of progression despite this therapy)
* At least 2 weeks since prior chemotherapy
* No more than 2 prior chemotherapy regimen for metastatic melanoma
* Prior therapies with vaccines, targeted agents not believed to affect the kit proteins, cytokines, interferon-α, or intratumoral injections will NOT be considered prior therapy unless administered with a chemotherapy drug
* No prior therapy with an inhibitor of the kit protein
* No other concurrent investigational agents
* No other concurrent anticancer agents or therapies
* No concurrent antiretroviral therapy for HIV-positive patients
* No concurrent inhibitors of CYP3A4, including any of the following:

  * Fluconazole, itraconazole, ketoconazole, macrolide antibiotics (azithromycin, clarithromycin, erythromycin, troleandomycin),midazolam, nifedipine, verapamil, diltiazem, terfenadine, cyclosporine and cisapride
  * Herbal extracts and tinctures with CYP3A4 inhibitory activity, including the following:

    * Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort),Uncaria tomentosa (cat's claw), Echinacea angustifolia roots, Trifolium pratense(wild cherry), Matricaria, chamomilla (chamomile), Glycyrrhiza glabra (licorice), dillapiol, hypericin, and naringenin
* No concurrent inducers of CYP3A4, including any of the following:

  * Carbamazepine, phenobarbital, phenytoin, and rifampin