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Cisplatin With or Without Sodium Thiosulfate in Treating Young Patients With Stage I, Stage II, or Stage III Childhood Liver Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00652132
First received: April 2, 2008
Last updated: August 9, 2013
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Liver Cancer
Ototoxicity
Drug: cisplatin
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
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 115
Study Start Date: December 2007
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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00652132

Locations
United Kingdom
Birmingham Children's Hospital Recruiting
Birmingham, England, United Kingdom, B4 6NH
Contact: Contact Person    44-121-333-8233    bruce.morland@bch.nhs.uk   
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   
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Contact Person    44-1223-348-151    amos.burke@addenbrookes.nhs.uk   
Great Ormond Street Hospital for Children Recruiting
London, England, United Kingdom, WC1N 3JH
Contact: Contact Person    44-20-7829-7924    brockp@gosh.nhs.uk   
Royal Marsden - London Recruiting
London, England, United Kingdom, SW3 6JJ
Contact: Contact Person    44-20-8661-3957    sucheta.vaidya@icr.ac.uk   
Royal Manchester Children's Hospital Recruiting
Manchester, England, United Kingdom, M27 4HA
Contact: Contact Person    44-161-922-2227    bernadette.brennan@cmmc.nhs.uk   
Queen's Medical Centre Recruiting
Nottingham, England, United Kingdom, NG7 2UH
Contact: Contact Person    44-115-924-9924    martin.hewitt@nuh.nhs.uk   
Sheffield Hallam University - City Campus Recruiting
Sheffield, England, United Kingdom, S1 1WB
Contact: Contact Person    44-114-271-7366    mary.gerrard@sch.nhs.uk   
Royal Aberdeen Children's Hospital Recruiting
Aberdeen, Scotland, United Kingdom, AB25 2ZG
Contact: Contact Person    44-1224-550-217    veronica.neefjes@nhs.net   
Royal Hospital for Sick Children Recruiting
Glasgow, Scotland, United Kingdom, G3 8SJ
Contact: Contact Person    44-141-201-0392    jairam.sastry@ggc.scot.nhs.uk   
Sponsors and Collaborators
Children's Cancer and Leukaemia Group
Investigators
Principal Investigator: Milind D. Ronghe, MD Royal Hospital for Sick Children
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00652132     History of Changes
Other Study ID Numbers: CCLG-LT-2007-03, CDR0000590649, EU-20833, EUDRACT-2007-002402-21, SIOP-CCLG-LT-2007-03
Study First Received: April 2, 2008
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
ototoxicity
childhood hepatoblastoma
stage I childhood liver cancer
stage II childhood liver cancer
stage III childhood liver cancer

Additional relevant MeSH terms:
Liver Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Site
Cisplatin
Sodium thiosulfate
Anti-Bacterial Agents
Anti-Infective Agents
Antidotes
Antineoplastic Agents
Antioxidants
Antitubercular Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Radiation-Sensitizing Agents
Sequestering Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014