Trial Information

A Multi-centre Open-label Randomised Phase III Trial of the Efficacy of Sodium Thiosulphate in Reducing Ototoxicity in Patients Receiving Cisplatin Chemotherapy for Standard Risk Hepatoblastoma

OBJECTIVES:

Primary

- To assess the efficacy of sodium thiosulfate (STS) to reduce the hearing impairment
caused by cisplatin chemotherapy.

Secondary

- To carefully monitor any potential impact of STS on response to cisplatin and survival.

- To assess the short- and long-term tolerability of the combination of STS and cisplatin

- To prospectively evaluate and validate biological, radiological and pathological
features of standard-risk hepatoblastoma for future risk adapted management

- To investigate the effect of STS on the formation of cisplatin-DNA adducts.

- To prospectively collect patient DNA specifically for the analysis of possible genetic
factors that may contribute to the development of treatment-related ototoxicity and
nephrotoxicity

OUTLINE: This is a multicenter study. Patients are stratified according to country, median
age (< 15 months vs ≥ 15 months), and PRETEXT tumor classification (I vs II vs III).
Patients are randomized to 1 of 2 treatment arms.

- Arm I (Neoadjuvant and adjuvant cisplatin): Patients receive cisplatin IV over 6 hours
on day 1. Treatment repeats every 2 weeks for 4 courses. Patients with progressive
disease after course 4 are taken off study. Patients without evidence of disease
progression proceed to surgery. Beginning within 3 weeks after surgery, patients
receive cisplatin IV over 6 hours on day 1. Treatment repeats every 2 weeks for 2
courses in the absence of disease progression or unacceptable toxicity.

- Arm II (Neoadjuvant and adjuvant cisplatin and sodium thiosulphate): Patients receive
cisplatin IV over 6 hours and sodium thiosulphate IV over 15 minutes (beginning 6 hours
after completion of cisplatin) on day 1. Treatment repeats every 2 weeks for 4 courses.
Patients with progressive disease after course 4 are taken off study. Patients without
evidence of disease progression proceed to surgery. Beginning within 3 weeks after
surgery, patients receive cisplatin IV over 6 hours and sodium thiosulphate IV over 15
minutes (as in neoadjuvant therapy) on day 1. Treatment repeats every 2 weeks for 2
courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection and tumor biopsies periodically for biological and
pharmacological studies consisting of biomarker analysis, gene expression profiling, IHC,
proteomic analysis, and gene rearrangement analysis. Patients undergo auditory evaluations
at baseline, and at the completion of study treatment or at an age of at least 3.5 years to
measure ototoxicity and hearing impairment.

After completion of study treatment, patients are followed periodically for at least 5
years.