Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 8
- 主要终点
- Evaluation of the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis.
研究概览
简要总结
The hypothesize of this research is that rapamycin is effective and well-tolerated in teenagers with familial adenomatous polyposis (FAP). Rapamycin could be effective in blocking the formation of adenomas and/or their evolution by decreasing their size and number. Researchers aim to assess the safety profile of rapamycin in FAP adolescents using a 2 low dose regimen.
详细描述
FAP is a rare genetic disease linked to mutations of APC gene. Adenomatous polyps appear around the age of 10 and will evolve into colic adenocarcinoma. To date, there is no effective treatment; 100% of patients will develop colorectal cancer before 40 years. This risk is addressed by regular colonoscopy monitoring, in order to propose a timely prophylactic colectomy.
Rapamycin (sirolimus) is a drug that targets the mTOR (mammalian target of rapamycin) protein involved in the PI3K-Akt signalling pathway downstream of PI3K. There are interactions between the PI3K-Akt pathway and the Wnt/APC/-catenin pathway that is hyperactivated in FAP. Rapamycin was used out of indication with efficacy and good tolerance in 2 adolescents whose parents had refused colectomy. Researchers recently demonstrated its effectiveness in a child with very severe juvenile polyposis. Data are also available in animals, but no proof-of-concept studies have been conducted in humans.
In France, Rapamycin use is allowed in adults with kidney transplantation and pulmonary lymphangioleiomyomatosis. However, it is used on children over the market. According to the literature and the field experience, the hypothesize is that a through level of 3-8 ng/ml should be effective in children with FAP, with a lower rate of adverse events.
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
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children aged 12 to 17 at time of inclusion.
- •Patients with colonoscopy for diagnosis or follow-up of FAP.
- •≥ 5 polyps (> 2 mm) at initial colonoscopy (V1).
- •Free and informed consent, signed by both holders of parental authority/legal representative, with the accord of the minor patient.
- •Affiliated with a social security scheme.
- •Patients of childbearing potential must agree to the use of a method of contraception during the study.
排除标准
- •Inability to understand the nature and goals of the study and/or communication difficulties observed by the investigator.
- •Contraindication to performing a colonoscopy.
- •< 5 polyps (>2 mm) registered during initial colonoscopy (V1).
- •Advanced disease with high-grade dysplasia adenoma or even adenocarcinoma in situ that should required colectomy
- •Signs of primary tuberculosis infection or respiratory infection
- •Any other medical or psychological condition deemed incompatible with the proper conduct of the study according to the investigator.
- •Contraindications to rapamycin use
- •Participation in other biomedical research
- •Deprivation of liberty of the legal guardians by judicial or administrative decision.
- •Pregnancy, breastfeeding
研究组 & 干预措施
Rapamycin
干预措施: Rapamycin (Drug)
结局指标
主要结局
Evaluation of the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis.
时间窗: For the entire duration of taking the experimental drug (rapamycin) and up to one month after stopping.
Monitoring of adverse events (EvI) and serious adverse events (SvIG). Particular attention will be paid to known adverse events attributable to rapamycin according to the summary of product characteristics (SmPC).
次要结局
- Evaluation of the effect of rapamycin on the number of polyps, on the entire colon and by segments (rectum, left colon, transverse colon and right colon) in adolescents suffering from Familial Adenomatous Polyposis(Visit 1 inclusion and 6 month after)
- Evaluation of the effect of rapamycin on the size of the largest polyp in each segment (rectum, left colon, transverse colon and right colon) in adolescents with Familial Adenomatous Polyposis(After 6 months of treatment with rapamycin)
- Evaluation of the effect of rapamycin on the size of polyps, on the entire colon and by segments (rectum, left colon, transverse colon and right colon) in adolescents suffering from Familial Adenomatous Polyposis.(Visit 1 inclusion and 6 month after)