Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose escalation trial as a weekly infusion for 3 consecutive weeks in patients with advanced solid tumours

Purpose: C-1311 is a member of the novel imidazoacridinone family of anticancer agents. This phase 1 trial was designed to investigate the safety, tolerability and preliminary anti-tumour activity of C-1311. Patients and methods: This was a phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous (IV) C-1311, administered weekly during 3 consecutive weeks followed by 1 week rest (constituting 1 cycle) in subjects with advanced solid tumours. Results: Twenty-two (22) patients were treated with C-1311, the highest dose given was 640 mg/m(2). All subjects experienced one or more treatment-related adverse events (AEs). The most frequently observed treatment-related AEs were neutropaenia and nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria for Adverse Events (CTCAE) grades 1-2, except for the blood and lymphatic system disorders, which were primarily of grades 3-4. The recommended dose (RD) of C-1311 administered as once weekly IV infusions for 3 weeks every 4 weeks is 480 mg/m(2), with the dose limiting toxicity (DLT) being grade 4 neutropaenia lasting more than 7 days. Treatment at this dose offers a predictable safety profile and excellent tolerability. Conclusion: The safety profile and preliminary anti-tumour efficacy of C-1311, observed in this broad-phase dose-finding study, warrants further evaluation of the compound. (C) 2009 Elsevier Ltd. All rights reserved.