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

NCT ID: NCT06308445

Last Updated: 2025-01-31

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2030-08-31

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin

Group Type: EXPERIMENTAL

Rapamycin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuel Mas, Pr

Role: STUDY_CHAIR

University Hospital, Toulouse

Locations

CHU Bordeaux Hôpital Pellegrin

Bordeaux, , France

CHU Montpellier Hôpital Arnaud de Villeneuve

Montpellier, , France

APHP Hôpital Robert Debré

Paris, , France

CHU Toulouse Hôpital des Enfants

Toulouse, , France

Countries

France

Central Contacts

Emmanuel Mas, Pr

Role: CONTACT

mas.e@chu-toulouse.fr

+33 5 34 55 84 45

Isabelle KIEFFER, CRA

Role: CONTACT

kieffer.i@chu-toulouse.fr

Facility Contacts

Raphael Enaud, Dr

Role: primary

raphael.enaud@chu-bordeaux.fr

+33 5 56 79 98 24

Laura Kollen, Dr

Role: primary

l-kollen@chu-montpellier.fr

+33 4 67 33 67 33

Jérôme VIALA, Pr

Role: primary

jerome.viala@aphp.fr

+33 1 40 03 36 83

Emmanuel Mas, Pr

Role: primary

mas.e@chu-toulouse.fr

+33 5 34 55 84 45

Other Identifiers

RC31/23/0388

Identifier Type: -

Identifier Source: org_study_id