SPARC study will apply innovative testing called “functional precision oncology”. It tests a small sample of each patient’s tumour at relapse or when it is treatment-refractory and provides detailed information on what combined medications the tumour is likely to respond to. SPARC partners have developed a testing platform that completes this analysis within impressive 7 days after a piece of the tumour was sampled. SPARC takes an innovative approach to selecting medications and designing treatments with better results and fewer side effects. The study will consider newer drugs that have never been used for soft tissue sarcoma, combining them based on what works best against each patient’s tumour sample. The study will also identify the dose that is effective against the tumour without causing too much harm to the patient.

To ensure the right treatment is available to the patients, SPARC will strive to implement “value-based treatment reimbursement”, a system in which medication cost is reimbursed for patients who benefit from them and is not restricted to a specific disease. The prospect of this system can be a game changer in future rare cancers trial design. After SPARC is completed, its strategy and process can be a blueprint for how to provide better treatment to other children with rare cancers.

The purpose of PerFoRM for Kids project is to evolve a novel precision medicine approach for children with osteosarcoma from basic science principles to “trial readiness” over the next four years. To achieve this, researchers will study how a newly developed drug, TH9619, targeting the way the body uses (metabolises) folate (vitamin B9) acts in paediatric osteosarcoma. The cells need folate to produce nucleotides – the building blocks they use to copy their DNA and divide. Unlike traditional chemotherapy, which attacks both healthy and cancerous cells, TH9619 acts as a « metabolic trap. » It specifically exploits the way cancer cells generate their building blocks, destroying the tumour while leaving healthy tissues unharmed. Because not all tumours are exactly the same, researchers will also validate a test for a biomarker (a specific biological indicator), called SHMT1. This will help them identify which patients will respond best to TH9619 therapy. For tumours that show an innate ability to resist the drug, researchers will develop a specialised two-drug combination to block their metabolic escape route.

Following the conclusion of this translational project researchers envision launching a paediatric Phase I/II clinical trial. In collaboration with industry partners and established European clinical networks, they will use the data generated as part of PerFoRM for Kids study to finalise the clinical trial protocol. The ultimate goal is to give children and adolescents with high-risk osteosarcoma rapid access to this promising new therapy improving their chances of survival while protecting them from the unnecessary toxicities of current treatments.