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

This is an interventional treatment trial for Metastatic Melanoma Read More

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.