Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 3
- 主要终点
- regression of radio-induced fibrosis (RIF) evaluated by high frequency ultrasound
研究概览
简要总结
Molecular mechanisms involved in radio-induced fibrosis are assessed in UPRES EA 27-10 since 10 years. Besides the canonical TGFbeta/ Smad pathway involved in radio-induced fibrosis (RIF), the Rho/ROCK/CTGF cascade has been shown to be also implicated in molecular mechanisms of RIF. Curative administration of Pravastatin or ROCK specific inhibitors inhibits the chronically activated Rho/ROCK/CTGF pathway in vitro in human cells lines and ex vivo in human samples. In addition, the curative administration of Pravastatin improves established RIF in vivo. The investigators data suggest that the pravastatin-based strategy is an efficient and safe antifibrotic therapy, easily transferable into the clinic to improve the quality of life of long-term cancer survivors without interfering with prior anticancer treatment.
This clinical trial evaluates the curative efficacy of Pravastatine in patients who presented a cutaneous and/ or subcutaneous fibrosis (grade >= 2 according to NCI-CTCAE v4 toxicities scale) and who were treated by radiotherapy for a head and neck cancer. Patients will be treated by Pravastatin during 12 months. An intermediate evaluation of efficacy by ultrasound will be assessed at 6 months and at last, at the end of the treatment. Patients assessment will be performed at 6 and 12 months after the end of the treatment to look at a potential rebound effect.
Objective(s) of the clinical study
Main objective: To assess Pravastatin efficacy in established cutaneous and subcutaneous radio-induced fibrosis revealed from 6 to 24 months after head and neck radiotherapy.
Second objective: To evaluate radio-induced fibrosis regression during the year following treatment stop.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Grade >= 2 cutaneous and/or subcutaneous fibrosis (NCI-CTCAE v4 toxicities scale) revealed from 6 to 24 months after head and neck radiotherapy.
- •Head and neck cancers treated by radiation therapy +/- chemotherapy, +/- surgery, with no evidence of progressive disease.
- •Karnofsky PS ≥ 70
- •normal renal function (plasmatic creatinine <= 130 micromol/l), normal cholesterol, normal hepatic function (total bilirubin <= 1.5 UNL, SGOT and SGPT <= 2 UNL)
- •Written informed consent of the patient.
排除标准
- •any chronic treatment by corticoids
- •severe cardiac pathology
- •patients already treated by statins or treated by fibrates, cyclosporine
- •history of muscular toxicities when treated by fibrates or by statins
- •Personal or familial history of hereditary muscular pathology
- •Plasmatic CPK >3 UNL
- •patient already included in another therapeutic trial with an experimental drug,
- •pregnant patient or susceptible to pregnancy or breast feeding (patients in age to give birth must be placed under efficient contraception),
- •a social or psychological condition that does not allow a positive patient's participation in the treatment and necessary medical follow-up to be envisaged,
- •the patient is under legal restrained or tutelage.
研究组 & 干预措施
Pravastatin
Pravastatin : 40mg/day during 12 months
干预措施: Pravastatin (Drug)
结局指标
主要结局
regression of radio-induced fibrosis (RIF) evaluated by high frequency ultrasound
时间窗: 12 months
a decrease of the maximal thickness more than 30% compared to RIF before treatment.
次要结局
- Fibrosis grade according to NCI-CTCAE v4 toxicities scale.(12 months)
- Quality of life(12 months)