A 2-stage controlled phase 1/2 study of STA-4783 in combination with paclitaxel in patients with advanced metastatic melanoma

7561 Background: STA-4783 (S), a novel inducer of heat shock protein 70 (hsp70) is a bis-thiobenzoylhydrazide compound. S leads to upregulation of hsp70 in tumor cell lines. Xenograft modeling with solid tumor cell lines demonstrated dramatic antitumor activity in combination with paclitaxel (P). Mechanistic studies suggest that the P enhancement is immune-mediated, creating, in effect, a chemically-induced biochemotherapy. The combination of S and P has been studied in a Phase 1 trial with the drugs coadministered i.v. over 3 h every 3 weeks. Doses ranged from (S/P, mg/m2) 44/135 to 525/175. Based on dose-related HSP70 induction (evidence of biological activity) and demonstrated tolerability, we began a Phase 2 study of the combination in patients with metastatic melanoma. Methods: The study consists of an initial safety assessment of the weekly dose schedule for 3 weeks every 4 weeks at S 106 mg/m2 and P 80 mg/m2. S was then escalated to 213 mg/m2 in combination. The higher tolerated dose level was expa...