Cisplatin With or Without Sodium Thiosulfate in Treating Young Patients With Stage I, II, or III Childhood Liver Cancer
Condition: Liver Cancer; Ototoxicity
MeSH terms: Liver Neoplasms; Hepatoblastoma; Ototoxicity
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the
      growth of tumor cells, either by killing the cells or by stopping them from dividing.
      Chemoprotective drugs, such as sodium thiosulfate, may protect normal cells from the side
      effects of chemotherapy. It is not yet known whether giving sodium thiosulfate is effective
      in reducing hearing damage caused by cisplatin in treating young patients with liver cancer.

      PURPOSE: This randomized phase III trial is studying how well sodium thiosulfate works to
      decrease hearing loss caused by cisplatin in treating young patients with stage I, stage II,
      or stage III childhood liver cancer.
    

Detailed description: 
      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.
    

Intervention name(s): cisplatin; sodium thiosulfate
Intervention type(s): Drug; Drug
Intervention MeSH terms: Sodium thiosulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ototoxicity; childhood hepatoblastoma; stage I childhood liver cancer; stage II childhood liver cancer; stage III childhood liver cancer