A National Phase I Study of Cabozantinib in Combination with 13-cis-Retinoic Acid in Children with Relapsed or Refractory Solid Tumors

Pediatric Cancers

Peter Zage (Rady)
Karen Messer (MCC)

Children with high-risk and recurrent solid tumors have extremely poor outcomes despite aggressive therapy, and new treatments are desperately needed. Growth factor receptors are proteins on the surfaces of cancer cells that generate signals leading to cancer cell growth and spread, and these receptors therefore represent potential targets for new treatments for many pediatric solid tumors. Cabozantinib is an inhibitor of several key growth factor receptors and kills pediatric solid tumor cells, and the effectiveness of cabozantinib is increased when combined with 13-cis-retinoic acid.

However, the safety and efficacy of the combination of cabozantinib with 13-cis-retinoic acid in children with solid tumors are unknown. We believe that cabozantinib and 13-cis-retinoic acid will be safe and effective in children with relapsed and refractory solid tumors and that children will have altered levels of specific proteins in their blood and tumor cells after cabozantinib treatment. We will test the combination of cabozantinib and 13-cis-retinoic acid in a national multi-institutional phase I clinical trial for children with relapsed and refractory solid tumors, including brain tumors, and we will also evaluate the levels of proteins in patient blood and tumor samples to determine their association with responses to treatment. The results from this proposed research will provide important information to evaluate a unique treatment combination that could improve the chances of survival in children with all forms of cancer.