Safety Study for the Use of Rapamycin in Children with Familial Adenomatous Polyposis (RAPA-4-PAF)

Toulouse University Hospital

Status and phase

Not yet enrolling

Phase 2

Conditions

Familial Adenomatous Polyposis

Treatments

Drug: Rapamycin

Study type

Interventional

Funder types

Other

Identifiers

NCT06308445

RC31/23/0388

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 estimated patients

Sex

All

Ages

12 to 17 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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