Evaluation of Mangafodipir Protective Activity Against Oxaliplatin Neurotoxicity
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection
研究概览
简要总结
Oxaliplatin is a major antitumor agent but its use is limited by potentially disabling neurotoxicity, characterized by a sensitive defect in the extremities.Mangafodipir is a MRI contrast agent with antioxidant properties. Our previous laboratory works showed that mangafodipir is able to prevent hematologic toxicity of several chemotherapy agents, including oxaliplatin and to increase their antitumor activity. Preliminary clinical data suggested that mangafodipir could prevent oxaliplatin neurotoxicity.The primary purpose of the present study is to assess the protective effect of mangafodipir in patients who have a already moderate oxaliplatin neuropathy and in whom the continuation of this treatment is desirable because of significant antitumor effect.
详细描述
Phase 2 study aiming to assess the protective effect of mangafodipir against the oxaliplatine neuropathy.Population: Cancer patient who have a mild (grade 2) oxaliplatin neuropathy and in whom the continuation of oxaliplatin for at least 4 infusions is desirable will be include, whatever the location of the primitive tumor and the use of others anticancer agents.Treatment: Mangafodipir (0.5 ml/kg) is administered as a 30 minutes infusion just after each administration of oxaliplatin. The oxaliplatin dose (85 to 100 mg/m²) and the length of the infusion (2 hours) are the same that before the inclusion and modifications are not authorized during all the study participation. Primary objective: Neuropathy are clinically evaluated according to NCI-CTC criteria before each mangafodipir and oxaliplatin and thereafter one month after the last infusion. The primary criteria is the worst grade of oxaliplatin neuropathy experienced by each patient. The improvement of neuropathy is defined as a decrease by at least one grade of the severity of the neuropathy for at least 2 months.
Hypothesis
at least 50% of patients will experience an improvement or a stabilization of the oxaliplatin neuropathy while receiving the mangafodipir - oxaliplatin association.Treatment discontinuation: the treatment will be stopped if the neuropathy worsened by at least one grade, in case of tumor progression, intolerable toxicity, and patient wish.
Number of patients: it will be determined according to a simplified Gehan procedure: The inclusions will be stopped if no objective response (neuropathy improvement) is observed among the first 9 evaluable patients. If at least one response is observed, 16 more evaluable patients will be include. The total number of patients will be between 9 and 30 patients, including non evaluable patients.
Pharmacokinetic: Serum and intra- erythrocytes manganese concentration will be evaluated before each mangafodipir infusion in order to detect accumulation Pharmacodynamic: plasmatic total antioxidant activity, superoxide dismutase activity and lipid peroxidation will be assessed at the first cycle: before and after the administration of oxaliplatin and just after the perfusion of mangafodipir.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •NCI CTC grade 2 or more neuropathy induced by oxaliplatine
- •At least 18 years old
- •ECOG PS: 2 or less
- •Life expectancy longer than 3 months
- •Written informed consent
- •Adequate hematologic, liver and renal functions
排除标准
- •Known hypersensibility to oxaliplatine
- •Cancer resistant to oxaliplatine
- •Fertile woman or man not willing to use adequate contraception
- •Pregnant or lactating women
- •Vitamin B6 administration within 48h prior to mangafodipir administration
- •Uncontrolled infection
- •Treatment with any other investigational agent, or participation in another clinical trial within 3 weeks prior to first administration of mangafodipir
- •Evidence of any other disease or condition that contra-indicates the use of an investigational drug
- •No Social Security insurance
研究组 & 干预措施
1
干预措施: Mangafodipir (Drug)
结局指标
主要结局
Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection
时间窗: every 15 days
次要结局
- Number of oxaliplatin administration(every 15 days)
- Progression free survival (time from inclusion to cancer progression)(6 months)