Phase II Single-Center Study of Bevacizumab in Combination With Temozolomide in Patients With First-Line Metastatic Uveal Melanoma
Phase II Single-Center Study of Bevacizumab in Combination With Temozolomide in Patients With First-Line Metastatic Uveal Melanoma
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving temozolomide together with bevacizumab may kill more tumor cells.
PURPOSE: This phase II trial is studying giving temozolomide together with bevacizumab to see how well they work in treating patients with metastatic melanoma of the eye.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive oral temozolomide once daily on days 1-7 and 15-21 and bevacizumab IV over 30-90 minutes on days 8 and 22. Treatment repeats every 28 days for up to 6 courses. Patients achieving at least stable disease then receive bevacizumab monotherapy IV every 2 weeks as maintenance therapy in the absence of unacceptable toxicity and disease progression. Patients undergo CT perfusion imaging at baseline, day 28, and at 3 and 6 months.
Blood samples are collected at baseline and then periodically for VEGF-A genetic polymorphism analysis.
After completion of study treatment, patients are followed up at 1 month.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed uveal melanoma
Measurable disease, defined as ≥ 1 measurable lesion as measured by RECIST criteria
No curative surgical treatment envisaged
No active brain metastases (if clinical suspicion, must have a brain CT scan within 28 days)
PATIENT CHARACTERISTICS:
WHO performance status (PS) 0-1 OR Karnofsky PS 70-100%
Life expectancy ≥ 12 weeks
Hemoglobin ≥ 10 g/dL
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR calculated creatinine clearance ≥ 50 mL/min
Proteinuria < 2+ on urinary dipstick OR 24-hour proteinuria ≤ 1 g
Total bilirubin ≤ 1.5 times ULN
AST/ALT ≤ 2.5 times ULN
Lactate dehydrogenase ≤ 5 times ULN
INR and PT ≤ 1.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No uncontrolled active disease or at risk of bleeding, ongoing infection, or clotting disorder
No other cancer except for skin carcinomas and cervical carcinoma in situ
No pre-existing peripheral neuropathy, > grade 2 (NCI CTC-AE)
No failure to comply with the medical follow-up of the study for geographical, social, or psychological reasons
No recent thrombophlebitis or pulmonary embolism within the past 6 months
No uncontrolled hypertension (systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg)
No concurrent active cardiovascular disease, uncontrolled by medical treatment within the past 6 months, including any of the following:
No unhealed wound, active peptic ulcer, bone fracture, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
No known hypersensitivity to bevacizumab, temozolomide, or their excipients
PRIOR CONCURRENT THERAPY: