Cisplatin With or Without Sodium Thiosulfate in Treating Young Patients With Stage I, II, or III Childhood Liver Cancer
SIOPEL6
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
4 other identifiers
interventional
116
1 country
16
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2007
Longer than P75 for phase_3
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 15, 2007
CompletedFirst Submitted
Initial submission to the registry
April 2, 2008
CompletedFirst Posted
Study publicly available on registry
April 3, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 4, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
February 28, 2018
CompletedMay 29, 2018
May 1, 2018
9.7 years
April 2, 2008
May 24, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of Brock grade ≥ 1 hearing loss
To investigate if the administration of sodium thiosulfate simultaneously with the administration of Cisplatin significantly reduces the hearing impairment
End of trial treatment or at an age of 3.5 years, whichever is later
Secondary Outcomes (8)
Response to preoperative chemotherapy
Following completion of preoperative chemotherapy
Complete resection
Within 2 weeks after surgery.
Complete remission
End of trial treatment
Event-free survival (EFS)
Until first event or up to 5 years
Overall survival (OS)
Until event or up to 5 years
- +3 more secondary outcomes
Study Arms (2)
Arm I (cisplatin)
ACTIVE COMPARATORNeoadjuvant 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 (cisplatin + STS)
EXPERIMENTALNeoadjuvant 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.
Interventions
Eligibility Criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
Birmingham Children's Hospital
Birmingham, England, B4 6NH, United Kingdom
Bristol Royal Hospital for Childre
Bristol, England, BS2 8AE, United Kingdom
Addenbrooke's Hospital
Cambridge, England, CB2 2QQ, United Kingdom
Royal Marsden - London
London, England, SW3 6JJ, United Kingdom
Great Ormond Street Hospital for Children
London, England, WC1N 3JH, United Kingdom
Royal Manchester Children's Hospital
Manchester, England, M27 4HA, United Kingdom
Queen's Medical Centre
Nottingham, England, NG7 2UH, United Kingdom
Sheffield Hallam University - City Campus
Sheffield, England, S1 1WB, United Kingdom
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, AB25 2ZG, United Kingdom
Royal Hospital for Sick Children
Glasgow, Scotland, G3 8SJ, United Kingdom
The Noah's Ark Children's Hospital for Wales
Cardiff, United Kingdom
Royal Hospital For Sick Children
Edinburgh, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Alder Hey Children's Hospital Trust
Liverpool, United Kingdom
John Radcliffe Hospital
Oxford, United Kingdom
Southampton Children's Hospital
Southampton, United Kingdom
Related Publications (1)
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.
PMID: 29924955DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Milind D. Ronghe, MD
Royal Hospital for Sick Children
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 2, 2008
First Posted
April 3, 2008
Study Start
December 15, 2007
Primary Completion
September 4, 2017
Study Completion
February 28, 2018
Last Updated
May 29, 2018
Record last verified: 2018-05