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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Extraocular Extension Melanoma; Recurrent Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Recurrent Intraocular Melanoma; Iris Melanoma; Stage IV Melanoma

Treatments: Drug: carboplatin; Drug: bortezomib; Drug: paclitaxel

Study type: Interventional

Funder types: NIH

Identifiers

NCT00288041

MC047C

NCI-2009-00138

N01CM62205 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This phase II trial is studying how well giving bortezomib together with paclitaxel and carboplatin works in treating patients with metastatic melanoma. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bortezomib may help paclitaxel and carboplatin kill more tumor cells by making tumor cells more sensitive to these drugs

Full description

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.

Enrollment: 36 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Treatment (bortezomib, paclitaxel, carboplatin)

Experimental group

Description:

Patients will receive an infusion of bortezomib twice in week 1 and once in week 2. They will also receive a 3-hour infusion of paclitaxel and an infusion of carboplatin once in week 1. Treatment may repeat every 3 weeks for as long as benefit is shown.

Treatment:

Drug: paclitaxel

Drug: bortezomib

Drug: carboplatin