There is no current gold standard chemotherapy option for children with relapsed hepatoblastoma or hepatoblastoma that does not respond to upfront chemotherapy. This study aims to broaden the collective knowledge about relapsed hepatoblastoma to better inform treatment options with the goal of long-term survival and health.
Cisplatin is the most effective medical therapy for hepatoblastoma at the time of initial diagnosis and has shown to be helpful at time of relapse (Somers et al, Manuscript submitted). It is important to understand how retreating children with cisplatin is tolerated with regards to toxicity, particularly hearing loss and renal function.
This trial will assess the effect of STS in preventing subsequent hearing loss when patients are re-challenged with cisplatin therapy at relapse/progression, as well as the efficacy of cisplatin/STS or cisplatin/STS/SAHA for patients with relapsed hepatoblastoma stratified by initial cisplatin sensitivity. The addition of SAHA (vorinostat; a histone deacetylase inhibitor) is based on an increasing amount of pre-clinical evidence in several hepatoblastoma laboratories demonstrating that HDAC inhibitors are active against hepatoblastoma, and can synergize with cisplatin making the tumor even more sensitive.
Thus, for patients who initially do not respond well to cisplatin, the addition of SAHA to cisplatin is being used to hopefully improve response and outcomes for such children.
Important pharmacokinetic measurements focused on cisplatin and STS in children, with varying degrees of renal function, will be assessed. Such pharmacokinetic data will fill a current gap in our clinical knowledge base and enable safer use of such agents for all children with such cancers, regardless of kidney function, in the future. In fact, poor renal function is a common reason for ‘ineligibility’ for the current COG study AHEP1531, and thus children with poor renal function are not afforded the opportunity for organized advancement of care on trials, given lack of cisplatin safety and dosing standards in such a situation.
Additionally, the study will collect data on the biology of relapsed/refractory hepatoblastoma tumors.
CSS is currently open to accrual at Cincinnati Children’s Hospital Medical Center with additional study sites to follow at Dana Farber Cancer Institute/Boston Children’s and University of California San Francisco. We welcome questions from interested families or clinicians! Please contact Dr. Jim Geller (firstname.lastname@example.org) and Dr. Kate Somers (Katherine.email@example.com) for further information.