Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 3105
© 2005 American Society of Clinical Oncology

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Abstract

Phase I trial of coramsine (SBP002) in patients with advanced solid tumors

Sir Charles Gairdner Hosp, Nedlands, Australia; Solbec Pharmaceuticals Ltd, Perth, Australia

3105

Background: Coramsine (SBP002) is a 1:1 mixture of solasonine and solamargine, plant glycoalkaloids found in the species Solanum linneanum, which have single agent and synergistic combination in vitro and in vivo preclinical efficacy in various tumor models through interaction with rhamnose-containing cell membrane glycoproteins and subsequent internalization. Methods: Coramsine as a 2 hour IV infusion daily x 5 every 2 weeks to define the MTD, recommended Phase II dose, toxicity and pharmacokinetics. Based on preclinical toxicology the infusion was increased to 4 hours at the MTD. Results: 19 previously treated advanced solid tumor pts with PS 0–2 were entered (melanoma 4, renal 4, sarcoma 2, mesothelioma 2, NSCLC 2, other 5). DLT occurred in 2/2 pts at 1.5mg/kg/day (2hr) and 2/2 pts at 3.0mg/kg/day (4hr). Limiting toxicity was grade III/IV transaminitis with grade I-II increases of bilirubin and creatinine. Hepatotoxicity was maximal at days 3–5, resolved over 10–21 days, was clinically asymptomatic apart from grade I-II fatigue, and was not cumulative. Preceding dose levels 1.0mg/kg (2hr) and 1.5mg/kg (4hr) produced DLT in 2/6 pts each with no grade IV toxicity. No myelosuppression or other serious drug-related toxicity was recorded. 3 pts had complications (sepsis, thrombosis) related to venous access devices. Minor responses were documented in 2 pts; renal - mediastinal nodes (prior interferon); unknown primary adenocarcinoma - abdominal nodes (prior platinum based chemotherapy) both at 1.0mg/kg/day over 2 hours and both received 12 cycles. Initial PK results indicate a terminal half-life of >12 hours for both solasonine and solamargine and peak levels of both >2,000ng/ml corresponding to active in vitro levels at doses >0.75mg/kg over 2 hours. Conclusions: On this schedule coramsine produces limiting hepatotoxicity at doses above 1.0mg/kg/day over 2 hours or 1.5mg/kg/day over 4 hours. 1.0mg/kg/day over 2 hours is suitable for Phase II. Some activity has been seen against resistant solid tumors. A continuous infusion schedule will be investigated.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Solbec