Temozolomide Plus Bevacizumab in Patients With Metastatic Melanoma Involving the Central Nervous System

Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed malignant melanoma and clinical evidence of metastatic disease to the brain. Mucosal and ocular melanomas are included. 2. Untreated asymptomatic brain metastases ≤ 2 cm in maximal diameter, with mild or minimal edema, without associated hemorrhage or midline shift. 3. Progressing brain metastases of any size, not amenable to surgical resection and/or progressing through radiation therapy but without evidence of active associated hemorrhage. Treatment with bevacizumab may not be initiated until 4 weeks after surgical resection or radiation therapy completion. 4. Hemorrhagic metastases that have resolved after previous resection or radiation therapy do not exclude patients with new non-hemorrhagic metastases meeting the criteria described above from participating. 5. Patients must have measurable metastases to the brain, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm in the brain MRI with gadolinium. For disease outside the brain, tumors must be \> 20 mm with conventional techniques or \> 10 mm with spiral CT scan. Measurable disease outside the brain is NOT required. 6. Patients with any number of previous systemic therapies are eligible. Previous temozolomide treatment given on a different schedule is allowed, as long as it had not been given in combination with VEGF-targeting drugs. 7. Age \> 18 years. Because no dosing or adverse event data are currently available on the use of bevacizumab in patients \<18 years of age, children are excluded from this study. 8. Life expectancy of 8 weeks or greater. 9. ECOG performance status \< 2 (Karnofsky \> 60%). 10. Patients must have normal organ and marrow function as defined below: * Leukocytes \> 3,000/µl * Absolute neutrophil count \> 1,500/µl * Platelets \> 100,000/µl * Total Bilirubin \*\* Within institutional upper limit of normal * AST(SGOT)/ALT(SGPT) \< 2.5 X institutional upper limit of normal * Creatinine\* Within institutional upper limit of normal\* * If creatinine \> upper limit of normal, a creatinine clearance \>/= 60 ml/m2 is required * Except for patients with known Gilbert's syndrome 11. The effects of bevacizumab on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because the anti-angiogenic agent used in this trial may be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 12. Concomitant use of steroids to treat cerebral edema is allowed. 13. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Disease-Specific Exclusions Patients with metastatic disease to the brain not fitting the inclusion criteria. Patients with leptomeningeal disease are not excluded. * General Medical Exclusions Subjects meeting any of the following criteria are ineligible for study entry: 1. Inability to comply with study and/or follow-up procedures. 2. Life expectancy of less than 8 weeks 3. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than this study. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or temozolomide. 5. Patients must not exhibit any clinical evidence of coagulopathy. The INR must be \< 1.5 and the values for PTT must be within normal limits. Anticoagulation is not allowed. 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, untreated cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Pregnant women are excluded from this study because bevacizumab is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab. These potential risks may also apply to other agents used in this study. 8. Otherwise well HIV-positive patients will be permitted to enroll on this trial. Bevacizumab-Specific Exclusions 1. Previous treatment with bevacizumab. 2. Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications) 3. Any prior history of hypertensive crisis or hypertensive encephalopathy 4. New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E) 5. History of myocardial infarction or unstable angina within 6 months prior to study enrollment 6. History of stroke or transient ischemic attack within 6 months prior to study enrollment 7. Significant vascular disease (e.g., aortic aneurysm, aortic dissection) 8. Symptomatic peripheral vascular disease 9. Evidence of bleeding diathesis or coagulopathy 10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study 11. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment 12. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment 13. Serious, non-healing wound, ulcer, or bone fracture 14. Proteinuria at screening as demonstrated by either * Urine protein:creatinine (UPC) ratio 1.0 at screening OR * Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).