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

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

NCT ID: NCT06308445

Condition: Familial Adenomatous Polyposis

Conditions: Official terms:
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Adenomatous Polyposis Coli
Sirolimus

Conditions: Keywords:
Safety use
rapamycin
prophylaxis
teenager

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Rapamycin
Description: 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.
Arm group label: Rapamycin

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.

Criteria for 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

Gender: All

Minimum age: 12 Years

Maximum age: 17 Years

Healthy volunteers: No

Locations:

Facility:
Name: CHU Bordeaux Hôpital Pellegrin

Address:
City: Bordeaux
Zip: 33076
Country: France

Contact:
Last name: Raphael Enaud, Dr

Phone: +33 5 56 79 98 24
Email: raphael.enaud@chu-bordeaux.fr

Investigator:
Last name: Raphaël ENAUD, MD
Email: Principal Investigator

Facility:
Name: CHU Montpellier Hôpital Arnaud de Villeneuve

Address:
City: Montpellier
Zip: 34295
Country: France

Contact:
Last name: Laura Kollen, Dr

Phone: +33 4 67 33 67 33
Email: l-kollen@chu-montpellier.fr

Investigator:
Last name: Laura KOLLEN, MD
Email: Principal Investigator

Facility:
Name: APHP Hôpital Robert Debré

Address:
City: Paris
Zip: 75019
Country: France

Contact:
Last name: Jérôme VIALA, Pr

Phone: +33 1 40 03 36 83
Email: jerome.viala@aphp.fr

Investigator:
Last name: Jérôme VIALA
Email: Principal Investigator

Facility:
Name: CHU Toulouse Hôpital des Enfants

Address:
City: Toulouse
Zip: 31300
Country: France

Contact:
Last name: Emmanuel Mas, Pr

Phone: +33 5 34 55 84 45
Email: mas.e@chu-toulouse.fr

Investigator:
Last name: Emmanuel MAS, MD
Email: Principal Investigator

Start date: August 1, 2024

Completion date: August 2029

Lead sponsor:
Agency: University Hospital, Toulouse
Agency class: Other

Source: University Hospital, Toulouse

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06308445