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

NCT ID: NCT00652132

Last Updated: 2018-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

116 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-12-15

Study Completion Date

2018-02-28

Brief Summary

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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

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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.

Conditions

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Liver Cancer Ototoxicity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm I (cisplatin)

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.

Group Type ACTIVE_COMPARATOR

cisplatin

Intervention Type DRUG

Arm II (cisplatin + STS)

Neoadjuvant and adjuvant cisplatin and sodium thiosulphate (STS): 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.

Group Type EXPERIMENTAL

cisplatin

Intervention Type DRUG

sodium thiosulfate

Intervention Type DRUG

Interventions

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cisplatin

Intervention Type DRUG

sodium thiosulfate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Standard risk hepatoblastoma (Pretext I,II,III)
* Age ≤ 18 years and \> 1 month
* Written informed consent and national/local ethics committee and regulatory approval
* Centre/country willing and able to organise audiometry at the minimum required quality standard and to provide the contact details of the Consultant Audiologist or Ear Nose and Throat Surgeon who will take the responsibility for seeing that this is done
* Ability to comply with requirements for submission of material for central review
* For females of child-bearing potential, a negative pregnancy test prior to study treatment is required.
* Any patient who is of reproductive age should agree to use adequate contraception for the duration of the trial.

Exclusion:

High risk hepatoblastoma

* Hepatocellular carcinoma
* Treatment starting more than 15 days from written biopsy report
* Abnormal renal function
* Any previous chemotherapy
* Recurrent disease
* Previous hypersensitivity to STS
* Patient unable to follow the protocol for any reason
Minimum Eligible Age

1 Month

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Childhood Liver Tumours Strategy Group - SIOPEL

UNKNOWN

Sponsor Role collaborator

University of Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Milind D. Ronghe, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Hospital for Sick Children

Locations

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Birmingham Children's Hospital

Birmingham, England, United Kingdom

Site Status

Bristol Royal Hospital for Childre

Bristol, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Royal Marsden - London

London, England, United Kingdom

Site Status

Great Ormond Street Hospital for Children

London, England, United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, England, United Kingdom

Site Status

Queen's Medical Centre

Nottingham, England, United Kingdom

Site Status

Sheffield Hallam University - City Campus

Sheffield, England, United Kingdom

Site Status

Royal Aberdeen Children's Hospital

Aberdeen, Scotland, United Kingdom

Site Status

Royal Hospital for Sick Children

Glasgow, Scotland, United Kingdom

Site Status

The Noah's Ark Children's Hospital for Wales

Cardiff, , United Kingdom

Site Status

Royal Hospital For Sick Children

Edinburgh, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Alder Hey Children's Hospital Trust

Liverpool, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Southampton Children's Hospital

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Brock PR, Maibach R, Childs M, Rajput K, Roebuck D, Sullivan MJ, Laithier V, Ronghe M, Dall'Igna P, Hiyama E, Brichard B, Skeen J, Mateos ME, Capra M, Rangaswami AA, Ansari M, Rechnitzer C, Veal GJ, Covezzoli A, Brugieres L, Perilongo G, Czauderna P, Morland B, Neuwelt EA. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018 Jun 21;378(25):2376-2385. doi: 10.1056/NEJMoa1801109.

Reference Type DERIVED
PMID: 29924955 (View on PubMed)

Other Identifiers

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CDR0000590649

Identifier Type: OTHER

Identifier Source: secondary_id

2007-002402-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SIOP-CCLG-LT-2007-03

Identifier Type: OTHER

Identifier Source: secondary_id

RG_09-205

Identifier Type: -

Identifier Source: org_study_id

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