A phase 2 trial of trabectedin in children with recurrent rhabdomyosarcoma, Ewing sarcoma and non-rhabdomyosarcoma soft tissue sarcomas: a report from the Children's Oncology Group.

PURPOSE: To determine the toxicity, efficacy and pharmacokinetics of trabectedin given over 24h every 3 weeks to children with recurrent rhabdomyosarcoma, Ewing sarcoma, or non-rhabdomyosarcoma soft tissue sarcomas. PATIENTS AND METHODS: Trabectedin was administered as a 24-h intravenous infusion every 21 days. Two dose levels were evaluated (1.3 and 1.5mg/m(2)) for safety; efficacy was then evaluated using a traditional 2-stage design (10+10) at the 1.5mg/m(2) dose level. Pharmacokinetics (day 1 and steady state) were performed during cycle 1.
RESULTS: Fifty patients were enrolled, eight patients at 1.3mg/m(2) and 42 at 1.5mg/m(2). Dose limiting toxicities (DLTs) in the dose finding component included fatigue and reversible GGT elevation in 1/6 evaluable patients at 1.3mg/m(2) and 0/5 at 1.5mg/m(2). Efficacy was evaluated in 42 patients enrolled at the 1.5mg/m(2) dose of whom 22% experienced reversible grade 3 or 4 toxicities that included AST, ALT, or GGT elevations, myelosuppression and deep venous thrombosis. One patient with rhabdomyosarcoma had a partial response and one patient each with rhabdomyosarcoma, spindle cell sarcoma and Ewing sarcoma had stable disease for 2, 3 and 15 cycles, respectively.
CONCLUSION: Trabectedin is safe when administered over 24h at 1.5mg/m(2). Trabectedin did not demonstrate sufficient activity as a single agent for children with relapsed paediatric sarcomas. Copyright Â