A Phase I/II Study of Daily Oral Dosing With Temozolomide and Sunitinib Malate for 6 Weeks of an 8-Week Cycle in Patients With Metastatic and Unresectable Locally-Advanced Malignant Melanoma

Inclusion Criteria:

- Histologically confirmed Stage IIIC unresectable cutaneous or mucosal melanoma with
measureable disease or stage IV cutaneous, mucosal or ocular melanoma with
measureable disease.

- ECOG performance status of 0-2

- age greater than or equal to 18 years

- ANC ≥ 1,500/µL

- Platelet count ≥ 100,000/µL

- Hemoglobin ≥ 10.0 g/dL

- Creatinine ≤ 2 times upper limit of normal (ULN)

- Total bilirubin ≤ 2 times ULN

- LDH ≤ 5 times ULN

- AST or ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)

- LVEF ≥ 50% on screening ECHO

- women of childbearing potential must have a negative urine or serum pregnancy test
upto 28 days prior to commencement of dosing.

- Fertile patients must use effective contraception during and for ≥ 6 months after
completion of study treatment

- Willing and able to comply with scheduled visits, treatment plans, laboratory tests,
and other study procedures

- before study entry , written informed consent must be obtained. Written informed
consent must be obtained from patient prior to performing any study related
procedures.

Exclusion Criteria

- pregnant or nursing

- any following within the past 12 months:

- Myocardial infarction

- Severe and/or unstable angina

- Coronary and/or peripheral artery bypass graft

- Symptomatic congestive heart failure

- Cerebrovascular accident or transient ischemic attack

- Pulmonary embolism

- ongoing cardiac dysrhythmias ≥ grade 2, according to NCI CTCAE v3.0

- prolonged QTc interval on baseline EKG

- uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg despite optimal
medical therapy)

- pre-existing thyroid abnormality with thyroid function that cannot be maintained in
the normal range with medication

- any known clinically uncontrolled infectious disease, including HIV positivity or
AIDS-related illness

- severe acute or chronic medical or psychiatric condition or laboratory abnormality
that may increase the risk associated with study participation or study drug
administration or may interfere with the interpretation of study results, and, in the
judgment of the investigator, would make the patient inappropriate for study entry

- prior chemotherapy for melanoma, except for chemotherapy given during isolated limb
perfusion for stage IIIC disease

- Prior adjuvant immunotherapy and/or immunotherapy for metastatic disease allowed

- prior major surgery, radiotherapy, or immunotherapy within 4 weeks of starting
therapy

- treatment with potent CYP3A4 inhibitors 7 days before study dosing

- treatment with potent CYP3A4 inducers 12 days before study dosing

- concurrent treatment on another clinical trial (Concurrent participation on
supportive care trials or non-treatment trials (e.g., quality-of-life trials)
allowed).

- concurrent chemotherapy, immunotherapy, biological therapy, or investigational drugs

- concurrent drugs with dysrhythmic potential, including any of the following:

- Terfenadine

- Quinidine

- Procainamide

- Disopyramide

- Sotalol

- Probucol

- Bepridil

- Haloperidol

- Risperidone

- Indapamide