Cisplatin With or Without Sodium Thiosulfate in Treating Young Patients With Stage I, Stage II, or Stage III Childhood Liver Cancer
Conditions
Liver Cancer - Ototoxicity
Conditions: official terms
Liver Neoplasms
Conditions: Keywords
ototoxicity, childhood hepatoblastoma, stage I childhood liver cancer, stage II childhood liver cancer, stage III childhood liver cancer
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: cisplatin Type: Drug
Name: sodium thiosulfate Type: Drug
Name: gene rearrangement analysis Type: Genetic
Name: microarray analysis Type: Genetic
Name: proteomic profiling Type: Genetic
Name: immunohistochemistry staining method Type: Other
Name: laboratory biomarker analysis Type: Other
Name: adjuvant therapy Type: Procedure
Name: neoadjuvant therapy Type: Procedure
Name: therapeutic conventional surgery Type: Procedure
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 18 Years
Minimum Age: N/A
Gender: Both
Criteria: DISEASE CHARACTERISTICS:

- Histologically confirmed standard-risk hepatoblastoma, meeting all of the following criteria:

- PRETEXT I, II or III disease

- Serum alpha-fetoprotein (AFP) > 100 μg/L

- No additional PRETEXT criteria

- Newly diagnosed disease

- Must start study treatment within 15 days of confirmed biopsy

- No high-risk hepatoblastoma meeting any of the following criteria:

- Tumor involving all 4 hepatic sections (PRETEXT IV)

- Any of the following additional PRETEXT criteria:

- Extrahepatic abdominal disease (E1, E1a, E2, E2a)

- Intraperitoneal hemorrhage or tumor rupture (H1)

- Distant metastases, any site (M1)

- Lymph node metastases (N1, N2)

- Involvement of the main portal vein (P2, P2a)

- Involvement of all three hepatic veins and/or the inferior vena cava (V3, V3a)

- No recurrent disease

- No hepatocellular carcinoma

- Must provide adequate material for central reviews (radiology, pathology, and audiology) and if feasible, for the tissue storage program

- Must have an available audiology center that can test children at minimum required quality standard

PATIENT CHARACTERISTICS:

- Glomerular filtration rate ≥ 75% of the lower limit of normal for age (≥ 60 mL/min for patients ≥ 2 years old)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to follow study protocol

- No prior hypersensitivity to sodium thiosulfate

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy
Locations
Birmingham Children's Hospital
Birmingham, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-121-333-8233 - bruce.morland@bch.nhs.uk
Institute of Child Health at University of Bristol
Bristol, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-117-342-8451 - antony.ng@UHBristol.nhs.uk
Addenbrooke's Hospital
Cambridge, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-1223-348-151 - amos.burke@addenbrookes.nhs.uk
Great Ormond Street Hospital for Children
London, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-20-7829-7924 - brockp@gosh.nhs.uk
Royal Marsden - London
London, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-20-8661-3957 - sucheta.vaidya@icr.ac.uk
Royal Manchester Children's Hospital
Manchester, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-161-922-2227 - bernadette.brennan@cmmc.nhs.uk
Queen's Medical Centre
Nottingham, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-115-924-9924 - martin.hewitt@nuh.nhs.uk
Sheffield Hallam University - City Campus
Sheffield, England, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-114-271-7366 - mary.gerrard@sch.nhs.uk
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-1224-550-217 - veronica.neefjes@nhs.net
Royal Hospital for Sick Children
Glasgow, Scotland, United Kingdom
Status: Recruiting
Contact: Contact Person - 44-141-201-0392 - jairam.sastry@ggc.scot.nhs.uk
Start Date
December 2007
Sponsors
Children's Cancer and Leukaemia Group
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page