The development of precision oncology approaches has been one of the major scientific advances to improve outcomes for children, adolescents and young adults (CAYA) with cancer by providing a greater understanding of the molecular basis of their cancers and offering insight into potential novel therapies. Across Canada, the ACCESS Driver Project, PROFYLE, offers genome and transcriptome sequencing and bioinformatic analyses for all CAYA patients with ‘hard-to-cure’ cancers. To date, more than 40 percent of patients sequenced through PROFYLE have had a potentially actionable finding identified.

However, there is no established mechanism for these patients with potentially actionable findings in Canada to receive a corresponding targeted treatment – primarily due to the lack of molecularly-informed clinical trials for CAYA cancer patients available. Although there has been an overall increase in the number of precision oncology platform trials in which multiple novel therapies can be simultaneously tested in relatively small patient populations, there remains a sparsity of platform trial opportunities for CAYA with cancer despite an increasingly demonstrated unmet need in this population. Furthermore, the few CAYA-specific precision oncology platform trials that do exist – stemming from the United States and Europe – have not opened at Canadian pediatric cancer centres due to regulatory challenges and limitations on drug distribution.

In collaboration with colleagues from ZERO Childhood Cancer in Australia, the OPTIMISE (Optimal Precision TherapIes to CustoMISE Care in Childhood and Adolescent Cancer) trial has been developed as a multi-arm platform trial that will develop and test novel therapies for eligible patients identified by multi-omic sequencing through a national CAYA cancer sequencing program, such as PROFYLE and ZERO Childhood Cancer.

The OPTIMISE trial will help facilitate the uptake of treatment recommendations from PROFYLE and ZERO Childhood Cancer, allowing the evaluation of novel molecular-targeted agents. We hope that this will ultimately lead to improved tumour response rates and progression-free survival for patients with relevant molecular findings, as well as an improved understanding of treatment response and resistance mechanisms of response. Thus, this trial will provide the crucial next step to the translation of advances in clinical genomics into the testing of innovative molecularly targeted therapies for CAYA patients with cancer in Canada.

The ACCESS Clinical Trials research theme is dedicated to facilitating greater participation across Canada in the OPTIMISE trial.  The trial will open at up to six Canadian centres and integrate the use of satellite sites, where possible, to minimize travel time for patients and families and enhance involvement from communities that have been historically underrepresented in clinical trials.

For more information, please contact Tricia Schneider.