Temozolomide and Sorafenib in Treating Patients With Metastatic or Unresectable Melanoma

INCLUSION CRITERIA

• Histologically or cytologically confirmed melanoma that is metastatic or unresectable.
• The following groups are eligible with regard to prior therapy in either the adjuvant or metastatic disease setting:

a) No prior therapy c) Immunotherapy consisting of Interferon, Interleukin-2 or GM-CSF. d) Chemotherapy, either single-agent or combination. Prior temozolomide is allowable e) Vaccine therapy f) Prior sorafenib is allowable

NB: There is no limit on the number of prior therapies

• Prior radiation therapy is allowed. However, if radiation has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions.
• Measurable disease by RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered. Baseline CT or MRI scans of disease sites must be performed within 4 weeks of study entry. For patients with bone metastases, a baseline bone scan must be performed within 4 weeks of study entry.
• Age > 18 years.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Baseline laboratory values (evaluated within 14 days of randomization):

White Blood Count > 3,000/mm3 Absolute Granulocyte Count > 1,500/mm3 Platelet Count > 100,000/mm3 Serum creatinine < 2.0 x upper limit of normal (ULN) or serum creatinine clearance estimated by the MDRD formula Total Bilirubin < 1.5 x ULN (< 3.0 x ULN in the presence of Gilbert's disease AST/ALT < 2.5 x ULN (< 5.0 ULN in the presence of liver metastases) INR < 1.5 and a PTT within the upper limit of normal (if on anticoagulation baseline INR before starting anticoagulation must be <1.5)

• Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.) or chemotherapy at least 4 weeks prior to entering the study and recovered from adverse events due to those agents. Patients must not receive any other investigational anticancer therapy during the period on study or the four weeks prior to entry, with the exception of vaccines.
• Patients with brain metastases must have completed radiation therapy if radiation is clinically indicated at the time of diagnosis and discontinued steroids prior to enrollment.
• The effects of sorafenib, temozolomide on the developing human fetus are unknown. For this reason and because antiangiogenic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately. If a man impregnates a woman while participatig in this study, he should inform his treating physician immediately as well.

EXCLUSION CRITERIA

• Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
• Patients must not have a serious intercurrent illness including, but not limited to, ongoing or active infection requiring parental antibiotics, clinically significant cardiovascular disease (e.g. uncontrolled hypertension, myocardial infarction, unstable angina), New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular disease within 1 year prior to study entry, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John's wort.
• Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to