A Phase 3 interventional study of cisplatin and sodium thiosulfate in Liver Cancer and Ototoxicity, sponsored by University of Birmingham. Completed at 16 sites in United Kingdom. Open to participants aged 1 Month to 18 Years. Per ClinicalTrials.gov, last updated 2018-05-29.
Sponsored by University of Birmingham · Phase 3, Interventional, and Treatment
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.
OBJECTIVES:
Primary
Secondary
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.
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.
1,345 studies on the registry are indexed under Liver Neoplasms; 335 are open to participants now.
This study's enrollment of 116 is above the median of 48 across 928 interventional studies indexed under Liver Neoplasms.
Browse Liver Neoplasms studies →University of Birmingham is the lead sponsor of 182 studies on the registry; 29 are open to participants now.
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Inclusion confirmed newly diagnosed hepatoblastoma
Exclusion:
High risk hepatoblastoma
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: cisplatin
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.
Drug: cisplatin · Drug: sodium thiosulfate
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
Time frame: End of trial treatment or at an age of 3.5 years, whichever is later
Response to preoperative chemotherapy
Defined as: Complete response (CR): no evidence of disease and normal serum AFP value (for age). Partial response (PR): any tumour volume shrinkage associated with a decreasing serum AFP value, \> 1 log below the original measurement. Stable disease (SD): no tumour volume change and no change, or \< 1 log fall of the serum AFP concentration. Progressive disease (PD): unequivocal increase in 1 or more dimensions and/or any unequivocal increase of the serum AFP concentration (three successive 1-2 weekly determinations) even without clinical (physical and/or radiological) evidence of tumour re-growth.
Time frame: Following completion of preoperative chemotherapy
Complete resection
Total macroscopic removal of the tumour as reported by the surgeon and pathologist. In case of any doubt the lack of residual tumour must be confirmed with imaging studies performed
Time frame: Within 2 weeks after surgery.
Complete remission
Lack of evidence of residual disease and normal (for age) alpha-foetal protein (AFP). To establish a complete remission all of the following requirements must be fulfilled: * No evidence of tumour intra-abdominally: negative abdominal (including hepatic) ultrasound or CT scan or Magnetic resonance imaging * No evidence of metastases: clear chest X-ray (PA and lateral) for non-metastatic patients. (Normal lung CT scan for patients with lung metastasis at diagnosis, who are high-risk by definition and not treated according to SIOPEL 6). * Serum AFP level either normal or compatible with age for at least 4 weeks after normalisation.
Time frame: End of trial treatment
Event-free survival (EFS)
Calculated from the time of randomisation to the first of the following events: progression, relapse, secondary primary malignancy or death.
Time frame: Until first event or up to 5 years
Overall survival (OS)
Calculated from the time of randomisation to death.
Time frame: Until event or up to 5 years
Toxicity as graded by CTCAE v 3.0
Adverse drug reactions are defined as adverse events, which are possibly, probably or definitely related to the trial treatment. They will be assessed according to NCI CTCAE v 3.0.
Time frame: 30 days post treatment
Long-term renal clearance
By clearance method either EDTA, iohexol or inulin.
Time frame: Until event or up to 5 years
Feasibility of central audiology review
The feasibility of central review
Time frame: End of trial treatment or at an age of 3.5 years, whichever is later
This study is completed, as verified in May 2018. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sodium thiosulfate