RO4929097 in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Melanoma That Can Be Removed by Surgery

Inclusion Criteria:

* Histologically or cytologically confirmed melanoma

  * Stage IIIB, IIIC, or IV disease
  * Disease that is deemed resectable by surgical consultation

    * Patients must agree to pretreatment biopsies of their tumor
* Measurable disease defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques OR as ≥ 10 mm by spiral CT scan

  * Measurable lesions must be deemed resectable
  * Skin metastases must be photographed and measured
  * No non-target disease
* No known brain metastases
* Life expectancy \> 3 months
* ECOG performance status 0-2 (Karnofsky 60-100%)
* WBC ≥ 3,000/mm³
* ANC ≥ 1,500/mm³
* Platelet count ≥ 75,000/mm³
* Hemoglobin \> 10 g/dL
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST and ALT ≤ 2.5 times ULN
* Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
* Fertile patients must agree to use 2 forms of contraception (i.e., barrier contraception and 1 other method of contraception) for ≥ 4 weeks prior to, during, and for ≥ 12 months post-treatment
* Negative pregnancy test
* Not pregnant or nursing
* No history of allergic reactions attributed to compounds of similar chemical or biological composition of gamma-secretase inhibitor RO4929097 or other agents used in the study
* No malabsorption syndrome or other condition that would interfere with intestinal absorption
* Able to swallow tablets
* No known history of hepatitis or have a history of liver disease or other forms of cirrhosis
* No uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, or hypokalemia despite adequate electrolyte supplementation
* No uncontrolled intercurrent illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia other than chronic
  * Unstable atrial fibrillation
  * Psychiatric illness and/or social situations that would limit compliance with study requirements
* No baseline QTcF \> 450 msec (male) or QTcF \> 470 msec (female)
* No history of cancer within the past 5 years except curatively treated basal or squamous cell cancer of the skin, in situ cervical cancer, or lobular carcinoma in situ of the breast
* No other concurrent anticancer agents or therapies
* More than 4 weeks since prior immunotherapy or local radiotherapy and recovered
* No prior chemotherapy for melanoma
* No concurrent medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)
* No concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
* No concurrent combination antiretroviral therapy for HIV-positive patients
* No concurrent ketoconazole or grapefruit juice while taking gamma-secretase inhibitor RO4929097
* No concurrent granulocyte colony-stimulating factors
* No other concurrent investigational agents