
    lack of accrual
  
['metastatic melanoma', 'brain metastases']
['nab-paclitaxel', 'temozolomide', 'bevacizumab']

        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.
      