Trial of eRapa to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance

Prior treatment

• Risk-reduction surgery (colectomy or partial colectomy) within the 12 months prior to screening.
• Use of non-steroidal anti-inflammatory drugs other than aspirin during the study. The use of 81 milligrams (mg) of aspirin a day or 650 mg of aspirin per week is allowed.
• Treatment with other FAP-directed drug therapy (including NSAID \[Non-steroidal anti-inflammatory drug\] drugs), unless completes a 4 week washout period prior to enrollment.
• Concurrent involvement in other clinical trials specifically evaluating chemoprevention in FAP.

Other illness

• Duodenum or colon/ rectum with high grade dysplasia or cancer on biopsy at screening.
• History of interstitial lung disease or non-infectious pneumonitis.
• Immunosuppressed state (e.g., HIV, use of chronic steroids), active, uncontrolled infection.

Lab values

• Serum creatinine or measured/ calculated creatinine clearance (or glomerular filtration rate \[GFR\]) \> 1.5 x ULN OR \< 30mL/min for participants with creatine levels \> 1.5 x institutional ULN. Bilirubin ≥ 1.5 x ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase \> 5 x ULN; ALT/AST \> 2 x ULN.
• INR or PT or aPTT \> 1.5 x institutional ULN unless the patient is receiving anticoagulant therapy as long as the PT or aPTT is within therapeutic range of intended use of anticoagulants.
• Patients with a colonic polyp burden too numerous to count.

Other

• Duodenal or colorectal polyp \> 1 centimeter (cm) not excised at the screening evaluation.
• Pregnancy or breast feeding.
• Unable to provide consent or anticipated inability to attend appropriate follow-up visits.
• Proteinuria \> 1+ on urinalysis or \> 1g/24h on 24h urine.
• On agents known to alter rapamycin metabolism significantly.

• Sign and date an informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, age at least 18 years at the time of consent.
• Phenotypic familial adenomatous polyposis (FAP) with disease involvement of the colorectum by either genetic or clinical diagnosis: Adenomatous polyposis coli (APC) germline mutation with or without family history, or with greater than a cumulative lifetime history of (\>) 100 adenomas in large intestine and a family history of FAP, or FAP phenotype post colectomy for polyposis with a family history of FAP. Minimum number of polyps required for enrollment is 10.
• Abilitiy to safely undergo endoscopy.
• Ability to take oral medication and be willing to adhere to the eRapa regimen.
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of eRapa administration.
• A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug.