Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer

OPTIMISE is an international clinical trial for children, adolescents and young adults with high-risk cancers, including central nervous system tumours, solid tumours and lymphomas. It builds on precision medicine programs in Australia (ZERO Childhood Cancer) and Canada (PROFYLE/KICS), which use advanced genetic testing (or “sequencing”) to identify changes in the tumour tissue that may be targeted with specific treatments.

OPTIMISE is known as an “adaptive platform trial”, meaning it can test several treatment options (called “arms”) under one central trial design. New arms can be added as promising drugs become available, and less effective treatments can be removed – allowing the trial to stay current and focused on the most effective therapies. Each arm targets a genetic pathway commonly altered in childhood cancers and is open to participants based on their tumour’s biology (such as the genetic changes detected), not the cancer type.

The first arm of OPTIMISE (Arm A) is testing paxalisib, a targeted drug that blocks the PI3K/AKT/mTOR gene pathway, in combination with chemotherapy drugs irinotecan and temozolomide. Arm A will assess the safety, best dose, and early signs of effectiveness of paxalisib and chemotherapy in children, adolescents and young adults with solid or brain tumours.