Cisplatin With or Without Sodium Thiosulfate in Treating Young Patients With Stage I, Stage II, or Stage III Childhood Liver Cancer
Recruitment status was Recruiting
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.
Drug: sodium thiosulfate
Genetic: gene rearrangement analysis
Genetic: microarray analysis
Genetic: proteomic profiling
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery
|Study Design:||Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Rate of Brock grade ≥ 1 hearing loss determined after end of trial treatment or at an age of at least 3.5 years [ Designated as safety issue: Yes ]
- Response to preoperative chemotherapy [ Designated as safety issue: No ]
- Complete resection [ Designated as safety issue: No ]
- Complete remission [ Designated as safety issue: No ]
- Event-free survival (EFS) [ Designated as safety issue: No ]
- Overall survival (OS) [ Designated as safety issue: No ]
- Toxicity as graded by CTCAE v 3.0 [ Designated as safety issue: Yes ]
- Long-term renal clearance [ Designated as safety issue: Yes ]
- Feasibility of central audiology review [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
- To assess the efficacy of sodium thiosulfate (STS) to reduce the hearing impairment caused by cisplatin chemotherapy.
- 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.
|Birmingham Children's Hospital||Recruiting|
|Birmingham, England, United Kingdom, B4 6NH|
|Contact: Contact Person 44-121-333-8233 firstname.lastname@example.org|
|Institute of Child Health at University of Bristol||Recruiting|
|Bristol, England, United Kingdom, BS2 8AE|
|Contact: Contact Person 44-117-342-8451 antony.ng@UHBristol.nhs.uk|
|Cambridge, England, United Kingdom, CB2 2QQ|
|Contact: Contact Person 44-1223-348-151 email@example.com|
|Great Ormond Street Hospital for Children||Recruiting|
|London, England, United Kingdom, WC1N 3JH|
|Contact: Contact Person 44-20-7829-7924 firstname.lastname@example.org|
|Royal Marsden - London||Recruiting|
|London, England, United Kingdom, SW3 6JJ|
|Contact: Contact Person 44-20-8661-3957 email@example.com|
|Royal Manchester Children's Hospital||Recruiting|
|Manchester, England, United Kingdom, M27 4HA|
|Contact: Contact Person 44-161-922-2227 firstname.lastname@example.org|
|Queen's Medical Centre||Recruiting|
|Nottingham, England, United Kingdom, NG7 2UH|
|Contact: Contact Person 44-115-924-9924 email@example.com|
|Sheffield Hallam University - City Campus||Recruiting|
|Sheffield, England, United Kingdom, S1 1WB|
|Contact: Contact Person 44-114-271-7366 firstname.lastname@example.org|
|Royal Aberdeen Children's Hospital||Recruiting|
|Aberdeen, Scotland, United Kingdom, AB25 2ZG|
|Contact: Contact Person 44-1224-550-217 email@example.com|
|Royal Hospital for Sick Children||Recruiting|
|Glasgow, Scotland, United Kingdom, G3 8SJ|
|Contact: Contact Person 44-141-201-0392 firstname.lastname@example.org|
|Principal Investigator:||Milind D. Ronghe, MD||Royal Hospital for Sick Children|