IRB Study Number 25-651
Status Recruiting
Locations Cleveland Clinic Weston Hospital , Cleveland Clinic Main Campus
Institute Digestive Disease & Surgery Institute
Description
This study is for adults with familial adenomatous polyposis (FAP) who are at high risk for disease progression and are under regular endoscopic surveillance.
The study is testing an oral medication called eRapa (encapsulated rapamycin) to see if it can delay disease progression compared with placebo (a look-alike capsule with no active drug). Disease progression includes things like development of cancer or high-grade dysplasia, needing major FAP-related surgery (such as colectomy or pouch removal), or a significant worsening of polyp burden in the colon, rectum, pouch, or duodenum.
Participants are randomly assigned (2:1) to receive either eRapa or placebo, taken by mouth once a day every other week. You will continue your usual FAP surveillance, including regular colonoscopy and upper endoscopy, and the study team will closely track your polyps, any surgeries, and your overall health.
Participation includes clinic visits, blood tests, questionnaires about quality of life, and endoscopies that are part of your routine FAP care, repeated at set intervals. Treatment continues until there is evidence of disease progression, you stop for any reason, or the trial ends
Inclusion Criteria
Age 18 years or older
Documented FAP, confirmed by:
a known APC gene mutation, or
a clear family history of FAP recorded in the medical record
Considered high risk for disease progression, defined as at least one of:
Intact colon with >100 but ≤500 polyps, or
Retained rectum/sigmoid or ileal pouch with ≥10 polyps that are ≥3 mm, or
Duodenal polyposis Spigelman stage 3 or 4 with ≥1 duodenal polyp ≥10 mm removed at baseline or within the last 18 months
Willing and able to undergo regular endoscopic evaluations (colon and/or upper endoscopy) as part of surveillance
Able to understand the study and sign informed consent
If you or your partner could become pregnant, you must be willing to use highly effective contraception during treatment and for about 12 weeks after the last dose, as required by the protocol
Exclusion Criteria
High-grade dysplasia or cancer in the duodenum, colon, rectum, or ileal pouch at screening endoscopy
Any polyp ≥8 mm left in place after screening endoscopy (all polyps ≥8 mm must be removed before starting)
Major surgery within the last 6 weeks
Another active cancer or a cancer diagnosed within the last 24 months, except for certain superficial skin cancers (basal or squamous cell)
Known immunodeficiency or current systemic immunosuppressive therapy (including significant daily steroid use)
Active serious infection, including tuberculosis, HIV, hepatitis B, or hepatitis C
Abnormal liver, kidney function, or blood counts that do not meet the safety thresholds for the trial (based on screening labs)
Use of FAP-directed drug therapy (chemoprevention medicines for FAP) within 6 weeks before the first dose
Regular low-dose aspirin or chronic NSAID therapy (beyond occasional pain use) within 4 weeks before the first dose
Prior pelvic radiation therapy
Use of strong CYP3A4/5 or P-gp inducers/inhibitors that cannot be safely stopped before and during the trial
Use of another investigational drug within 4 weeks or 5 half-lives (whichever is shorter) before screening, or participation in another interventional clinical trial
Significant protein in the urine or lipid abnormalities on screening labs that do not meet trial safety criteria
Any medical or social condition that, in the investigator’s opinion, would increase risk, prevent adherence to visits/procedures, or confound the trial results
