Open-label, multicenter, phase II trial of ABI-007 in previously treated and previously untreated patients with metastatic malignant melanoma

Abstract

7558 Background: ABI-007 (Abraxane TM), is an albumin-bound, nanoparticle form of paclitaxel with an improved therapeutic index that may be related to biological interactions with endogenous albumin receptors (eg, gp60) and binding proteins (eg, SPARC). The albumin-binding protein SPARC (osteonectin) was overexpressed in primary and metastatic malignant melanomas but not in normal melanocytes (Ledda et al, J Invest Derm 108:210, 1997) and was a predictor of clinical outcome in thin melanomas (Massi et al, Human Path 30:339, 1999). Methods: We conducted a Phase II study of ABX administered weekly for 3 weeks q4w without premedication in chemotherapy-naive (CN) (150 mg/m2) and previously treated (PT) (100 mg/m2) patients (pts) with measurable metastatic malignant melanoma (MMM). Results: 13 CN and 36 PT pts have been enrolled; 11 CN and 13 PT pts are currently evaluable for toxicity and response. Median age was 59 (range, 32–79); median number of metastatic sites was 2 (range, 1–8); median ECOG PS was 0 (range, 0–1). 8 CN and 12 PT pts had visceral involvement. The median number of monthly cycles received was 4 (range, 2–6) for CN pts and 4 (range, 1–6) for PT pts. 9 CN and 25 PT pts are continuing treatment. 84% (CN) and 92% (PT) of cycles were given without dose modification. No treatment-related (TR) deaths or TR grade (G) 4 toxicities occurred; no cases of febrile neutropenia were reported. TR G3 toxicities included fatigue (13%); neutropenia (13%); leukopenia (8%); rash (8%); alopecia, anemia, infection, lymphedema, motor neuropathy, and tumor pain (4% each). 3 CN and 9 PT pts have progressive disease. 2 CN pts have achieved a partial response; 1 additional CN and 4 PT pts with stable disease have continued on ABX without progression for >/= 24 weeks. Conclusions: ABX was well tolerated and resulted in long-term disease control in patients with MMM, some of whom had rapidly progressive disease while on previous therapy. Final study results will be presented. However, based on these encouraging early results in pts with aggressive visceral disease, further studies with ABX in MMM are being considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American BioScience American BioScience