Combo of Abraxane, TMZ, Bevacizumab in Metastatic Melanoma With Brain Metastases

Inclusion Criteria:

- Histologically or cytologically confirmed malignant melanoma and clinical evidence of
metastatic disease to the brain. Mucosal and ocular melanomas are included.

- Newly developed inoperable brain metastases without associated hemorrhage or midline
shift.

- Inoperable or metastatic extra cranial stage III or IV disease.

- Diagnostic quality MRI of the brain or if contraindicated then contrast CT scan of
the head performed within 28 days prior to registration.

- 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/CT scan.

- CT scan chest, abdomen and pelvis or PET CT scan performed within 28 days of study
registration. For disease outside the brain, tumors must be > 10 mm by CT scan.

- Prior therapy allowed but no prior therapy with nab-paclitaxel, paclitaxel,
temozolomide, DTIC or bevacizumab.

- Bevacizumab may not be initiated until 4 weeks after surgical resection or radiation
therapy completion.

- Age 18 or older.

- Pre-existing peripheral neuropathy must have < Grade 2 (per CTCAE 4.0) at the time of
registration.

- Negative serum or urine β-hCG pregnancy test at screening for patients of
childbearing potential.

- Women of childbearing potential and sexually active males must use an effective
contraception method during treatment and for three months after completing
treatment.

- ECOG Performance status 0-1.

- Estimated life expectancy of greater than 2 months.

- Patients must have adequate organ function as defined below (these must be evaluated
within 14 days prior to registration):

- leukocytes >3,000/mcL

- absolute neutrophil count >1,500/mcL

- platelets >100,000/mcL

- Hemoglobin >9.0 g/dL

- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit

- Alkaline phosphatase <2.5 X institutional upper limit

- Total bilirubin <1.5 X institutional upper limit of normal (unless associated with
Gilbert's syndrome)

- serum creatinine < 1.5 mg/dL OR 1.5 x institutional normal

- LDH there is no restriction

- INR <1.5 PTT WNL

- Urine protein (UPC) ratio 1.0 OR

- Urine dipstick for proteinuria. 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).

- Able to render informed consent.

Exclusion Criteria:

- Prior surgical resection for brain metastases.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bevacizumab, nab-paclitaxel or temozolomide.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring parenteral antibiotics, symptomatic congestive heart failure,
unstable angina pectoris, untreated cardiac arrhythmia and peripheral vascular
disease.

- History of myocardial infarction or unstable angina within 6 months prior to Day 1.

- History of stroke or transient ischemic attack within 6 months prior to Day 1.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to study screening.

- Serious, non-healed wound, ulcer, or bone fracture.

- History of hepatitis B, C or HIV.

- Uncontrolled hypertension or chronic renal disease. No known bleeding diathesis.

- Known hypersensitivity to human albumin.

- Surgery within 4 weeks of study registration. Must be fully recovered and fully
healed from any prior surgery.

- Patients having chemotherapy or extra cranial radiotherapy within 4 weeks prior to
study screening or those who have not recovered from adverse events due to agents
administered more than 4 weeks prior to the completion of study screening.

- Evidence of other concurrent active malignancy.

- Pregnant or nursing.

- Not be receiving any other investigational agent.