NCT06308445

Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis

Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis.

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 12 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Familial Adenomatous Polyposis

Interventions

Type	Name	Description
DRUG	Rapamycin	This is a 2-dose rapamycin safety study, with a target through level of 3 to \<5 ng/ml for the first 3 months and 5-8 ng/ml for the next 3 months for each of the included patients. To avoid the possible cumulative effect, the two treatment phases will be separated by a 3-weeks wash-out period.

Timeline

• Start date: 2025-08-01
• Primary completion: 2030-08-01
• Completion: 2030-08-01
• First posted: 2024-03-13
• Last updated: 2025-01-31

Locations

4 sites across 1 country: France