Bevacizumab and Temozolomide or Bevacizumab and Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed by Surgery
RATIONALE: Drugs used in chemotherapy, such as temozolomide, paclitaxel albumin-stabilized nanoparticle formulation, and carboplatin, 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. It is not yet known whether bevacizumab is more effective when given together with temozolomide or paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in killing malignant melanoma cells.
PURPOSE: This randomized phase II trial is studying the side effects of giving temozolomide together with bevacizumab and to see how well it works compared with giving bevacizumab together with paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in treating patients with stage IV malignant melanoma that cannot be removed by surgery.
Drug: paclitaxel albumin-stabilized nanoparticle formulation
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma|
- Progression-free survival at 6 months [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
- Toxicity as measured by NCI CTCAE version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Tumor response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Percent change in number of T, B, NK and dendritic cells from baseline [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Percent change in plasma concentrations of IL-1β, IL-1rα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, and VEGF from baseline [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||August 2008|
|Study Completion Date:||November 2012|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.
Given IV over 30-90 minutesDrug: temozolomide
Oral temozolomide on days 1-5
Experimental: Arm II
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.
Given IV over 30-90 minutesDrug: carboplatin
Given IV over 30 minutesDrug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV over 30 minutes
- To assess the anti-tumor activity, in terms of the percentage of patients who are treated with these regimens and who are progression-free at 6 months.
- To assess the safety profile of each treatment regimen.
- To estimate the response rate in patients treated with these regimens.
- To estimate the distribution of progression-free survival time and overall survival time of patients treated with these regimens.
- To examine the impact of therapy on angiogenesis and immune homeostasis.
OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1) and location of metastatic disease (M1a [skin or subcutaneous tissue or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. (closed to accrual 8/21/09)
- Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for VEGF plasma levels and analysis of changes in immune homeostasis.
Beginning at study entry, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00626405
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|Study Chair:||Svetomir Markovic, MD, PhD||Mayo Clinic|