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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 16
- 主要终点
- Rate of Brock grade ≥ 1 hearing loss
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: cisplatin (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.
干预措施: cisplatin (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.
干预措施: sodium thiosulfate (Drug)
结局指标
主要结局
Rate of Brock grade ≥ 1 hearing loss
时间窗: End of trial treatment or at an age of 3.5 years, whichever is later
To investigate if the administration of sodium thiosulfate simultaneously with the administration of Cisplatin significantly reduces the hearing impairment
次要结局
- Complete remission(End of trial treatment)
- Long-term renal clearance(Until event or up to 5 years)
- Toxicity as graded by CTCAE v 3.0(30 days post treatment)
- Feasibility of central audiology review(End of trial treatment or at an age of 3.5 years, whichever is later)
- Overall survival (OS)(Until event or up to 5 years)
- Event-free survival (EFS)(Until first event or up to 5 years)
- Response to preoperative chemotherapy(Following completion of preoperative chemotherapy)
- Complete resection(Within 2 weeks after surgery.)