Inclusion Criteria:

- Patients must have histologically or cytologically MSKCC confirmed recurrent or
metastatic melanoma

- Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1
dimension (longest diameter to be recorded), meeting 1 of the following criteria:

- Lesion > 10 mm by CT scan, MRI, or caliper measurement by clinical exam

- Lymph nodes > 15 mm in short axis by CT scan or MRI

- Lesion > 20 mm by chest X-ray

- Patient with accessible tumor must agree to undergo pre- and post-treatment tumor
biopsies

- No known brain metastases

- Patients with resected or successfully treated brain metastases with
stereotactic radiosurgery and who have been free from recurrence or progression
for ≥ 3 months allowed

- Life expectancy > 3 months

- ECOG performance status 0-2 (Karnofsky 60-100%)

- WBC ≥ 3,000/mm³

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Total bilirubin normal

- AST and ALT ≤ 3 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Fertile patients must use 2 forms of effective contraception ≥ 4 weeks before,
during, and for ≥ 12 months after completion of study treatment

- Negative pregnancy test

- Not pregnant or nursing

- Able to swallow tablets

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to gamma-secretase inhibitor RO4929097 or other agents used in
this study

- No malabsorption syndrome or other condition that would interfere with intestinal
absorption

- Not serologically positive for hepatitis A, B, or C and have an active infection, a
history of liver disease, or other forms of hepatitis or cirrhosis

- No uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia,
hyponatremia, hypophosphatemia, or hypokalemia, defined as less than the lower limit
of normal for the institution, 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

- A history of torsades de pointes or other significant cardiac arrhythmias other
than chronic, stable atrial fibrillation that require antiarrhythmics or other
medications known to prolong QTc

- No psychiatric illness and/or social situations that would limit compliance with
study requirements

- Patients who have had another cancer allowed provided there is convincing evidence
that melanoma is the disease requiring therapeutic intervention

- No QTcF > 450 msec (male) or > 470 msec (female)

- No concurrent food that may interfere with gamma-secretase inhibitor RO4929097
metabolism, including ketoconazole and grapefruit juice

- Recovered from prior therapy to < grade 2 toxicities as assessed by NCI CTCAE

- One prior systemic therapy for recurrent or metastatic disease allowed

- No prior cisplatin, vinblastine, temozolomide, dacarbazine, or a gamma-secretase
inhibitor

- At least 3 weeks since prior systemic therapy (6 weeks for carmustine, nitrosoureas,
or mitomycin C)

- At least 5 half-lives since prior small molecule-targeted therapy

- At least 6 weeks since prior anti-CTLA4 antibody

- No other concurrent investigational agents

- No concurrent medications with narrow therapeutic indices that are metabolized by
cytochrome P450 (CYP450), including warfarin sodium (Coumadin®)

- No concurrent strong inducers/inhibitors or substrates of CYP3A4, including
indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, and
nefazodone

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent anticancer agents or therapies