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
Last updated: 03/04/2013
NCT ID: NCT00288041
IRB Number:1300-05
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