Familial Adenomatous PolyposisPhase 2RAPA-4-PAFNCT06308445
Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis
A Phase 2 study testing Rapamycin in people with Familial Adenomatous Polyposis, run by University Hospital, Toulouse at 4 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Familial Adenomatous Polyposis
- What is being tested?
- Rapamycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesFrance
- Study dates
- 1 Sep 2026to Sep 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- Contraindications to rapamycin use
- Participation in other biomedical research
- Deprivation of liberty of the legal guardians by judicial or administrative decision.
- Pregnancy, breastfeeding
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Isabelle KIEFFER, CRA contact
France4 sites
CHU Bordeaux Hôpital Pellegrin
Bordeaux, 33076
Raphael Enaud, Dr, +33 5 56 79 98 24, raphael.enaud@chu-bordeaux.fr
Raphaël ENAUD, MD
CHU Montpellier Hôpital Arnaud de Villeneuve
Montpellier, 34295
Laura Kollen, Dr, +33 4 67 33 67 33, l-kollen@chu-montpellier.fr
Laura KOLLEN, MD
APHP Hôpital Robert Debré
Paris, 75019
Jérôme VIALA, Pr, +33 1 40 03 36 83, jerome.viala@aphp.fr
Jérôme VIALA
CHU Toulouse Hôpital des Enfants
Toulouse, 31300
Emmanuel Mas, Pr, +33 5 34 55 84 45, mas.e@chu-toulouse.fr
Emmanuel MAS, MD
About this study
Official title: Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis.
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.
Read the 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
- Being tested
- Rapamycin
- Keywords
- Safety use, rapamycin, prophylaxis, teenager
- Medical subject headings
- Adenomatous Polyposis Coli
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Rapamycin | Experimental | Not described Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis.
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).
Measured: For the entire duration of taking the experimental drug (rapamycin) and up to one month after stopping.
Secondary outcomes (3)
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
Analysis of the colonoscopies individually, blinded to the identity of the patient and the temporality of the colonoscopy in relation to the treatment, allowing a descriptive analysis of the number of polyps per segment (rectum, left colon, transverse colon, right colon).
Measured: Visit 1 inclusion and 6 month after
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.
Analysis of the colonoscopies individually, blinded to the identity of the patient and the temporality of the colonoscopy in relation to the treatment, allowing a descriptive analysis of the size of polyps per segment (rectum, left colon, transverse colon, right colon).
Measured: 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
Colonoscopies will be analyzed in a paired manner for each patient (before treatment / after treatment) in order to be able to make a more specific judgment of the evolution of the polyps.
Measured: After 6 months of treatment with rapamycin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2024
- Study start1 Sep 2026 (estimated)
- Primary completionSep 2030 (estimated)
- Study completionSep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial Adenomatous PolyposisStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuel Mas, Pr, Study chair, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06308445
- Sponsor's protocol ID
- RC31/23/0388
- Acronym
- RAPA-4-PAF
- Status last verified
- May 2026
- First submitted
- 22 Feb 2024
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety Study for the Use of Rapamycin in Children With Familial Adenomatous Polyposis.
- ClinicalTrials.gov ID
- NCT06308445
- Acronym / sponsor ID
- RAPA-4-PAF / RC31/23/0388
- Conditions
- Familial Adenomatous Polyposis
- Keywords
- Safety use, rapamycin, prophylaxis, teenager
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- Sep 2030 (estimated)
- Study completion
- Sep 2030 (estimated)
- First posted
- 13 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rapamycin | Experimental | Drug: Rapamycin |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RapamycinThis 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. | Drug | Rapamycin |
Primary outcome
Evaluation of the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis.
Time frame: 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).
3 secondary outcomes
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
Time frame: Visit 1 inclusion and 6 month after
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.
Time frame: 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
Time frame: After 6 months of treatment with rapamycin
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Isabelle KIEFFER, CRA contact
Emmanuel Mas, Pr study chair
University Hospital, Toulouse
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rapamycin in people with Familial Adenomatous Polyposis, run by University Hospital, Toulouse at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Emmanuel Mas, Pr (+33 5 34 55 84 45, mas.e@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of the safety profile of two doses of rapamycin in adolescents with Familial Adenomatous Polyposis. (time frame: For the entire duration of taking the experimental drug (rapamycin) and up to one month after stopping.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.