A Phase I Study of PS-341 (Bortezomib, Velcade) and Interferon-alpha-2b in Malignant Melanoma.
The primary objective of this study is to:
• Determine the safety, tolerability and DLTs of VELCADE when administered in combination
with interferon-alpha-2b (IFN-α-2b) to patients with metastatic malignant melanoma.
The secondary objectives of this study are to:
- Document any objective anti-tumor responses that may occur in response to this
- Document the time to tumor progression in patients receiving this treatment regimen.
- Measure levels of the cell cycle proteins p21 and p27 in PBMCs and tumor biopsies
obtained pre-study and during week 4 of Cycle 1 (Day 26).
- Conduct histologic evaluations of microvessel density, tumor apoptosis and lymphocytic
infiltrates within tumor biopsies obtained pre- and post-study.
- Measure plasma levels of bFGF and VEGF over the course of the study.
- Monitor the effects of proteasome inhibition on the biological activity of IFN-α within
immune cells by measuring Jak-STAT signal transduction in patient PBMCs.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine dose limiting toxicities (DLTs) of VELCADE when administered in combination with IFN-α-2b to patients with metastatic malignant melanoma.
A standard method for the design of this study. Initially, three patients will be treated at a starting dose of VELCADE (1.0 mg/m2). If one of the three patients demonstrates a DLT, then an additional 3 patients will be treated at that dose level. If only one of the six show DLT, then the next cohort of three patients will be entered at the next dose level (1.3 mg/m2). If two or more of the six demonstrate DLT, no further patients will be treated at that dose level. The highest dose level at which less than 2 patients experienced DLT will be expanded to six patients.
up to 25 weeks or until disease progression
William Carson, MD
Ohio State University
United States: Institutional Review Board
|Ohio State University||Columbus, Ohio 43210|