Bortezomib, Paclitaxel, and Carboplatin in Treating Patients With Metastatic Melanoma

PRIMARY OBJECTIVE:

I. Determine the confirmed tumor response rate and adverse event profile of bortezomib, carboplatin, and paclitaxel as first-line therapy for patients with metastatic melanoma.

SECONDARY OBJECTIVE:

I. Evaluate time to tumor progression, overall survival, and duration of response.

OUTLINE: This is a multicenter study.

Patients receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, and 8 and paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 2. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 3 years.

Criteria:

• No uncontrolled intercurrent illness including any of the following: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia
• No psychiatric illness that would limit compliance with study requirements
• No other uncontrolled serious medical conditions (e.g., diabetes)
• No more than 1 prior cytotoxic chemotherapy regimen
• No more than 2 prior immunotherapy regimens either in adjuvant or metastatic setting
• At least 4 weeks since prior major radiotherapy or chemotherapy
• At least 8 weeks since prior monoclonal antibody therapy
• At least 4 weeks since prior immunotherapy or biologic therapy
• At least 3 weeks since prior surgery
• Recovered from prior therapies
• No prior therapy with bortezomib, paclitaxel, or carboplatin
• No other prior or concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy or supportive care considered investigational
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent prophylactic colony-stimulating factors
• Histologically confirmed malignant melanoma
• Patients with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the principal investigator
• No known brain metastases by brain imaging with contrast
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Routine urine analysis with predicted 24-hour urine protein < 500 mg OR 1+ proteinuria by urine dipstick with 24-hour urine protein < 500 mg
• Total bilirubin < 1.5 mg/dL
• AST =< 3 times ULN
• Creatinine =< 1.5 times ULN
• ECOG performance status (PS) 0, 1, or 2 (Karnofsky PS >= 60%)
• Life expectancy by physician estimate > 12 weeks
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• Negative pregnancy test
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib
• No peripheral neuropathy >= grade 2
• Manifestations of stage IV disease (e.g., cutaneous, uveal)
• All melanomas, regardless of origin, allowed
• Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as >= 2.0 cm with conventional techniques or as >= 1.0 cm with spiral CT scan
• No nonmeasurable disease only, including any of the following: bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusion, inflammatory breast disease, lymphangitis cutis/pulmonis, abdominal masses that are not confirmed and followed by imaging techniques, cystic lesions
• Hemoglobin >= 9.0 g/dL