Sirolimus and Familial Adenomatous Polyposis (FAP)

Inclusion Criteria

• ≥ 18 years
• A genetically confirmed APC mutation
• Classical FAP phenotype (100-1000 colorectal adenomatous polyps)
• Subtotal colectomy with ileorectal anastomosis (IRA) or total colectomy with ileo-anal pouch anastomosis (IPAA)
• Severe rectal or pouch polyposis, defined as having >25 polyps amenable to complete removal (InSiGHT 2011 Staging System score of 3)
• Fertile patients must use effective contraception during study treatment and until 12 weeks after study treatment

Exclusion Criteria

• Inability to give informed consent
• Participation in another interventional clinical trial
• Subjects who are pregnant or breast-feeding, proved with a negative pregnancy test if female of child-bearing potential
• Prior pelvic irradiation
• Invasive malignancy in the past 5 years
• Subjects who are HIV positive
• Subjects with severe systemic infections, current or within 2 weeks prior to study start
• Subjects with known severe restrictive or obstructive pulmonary disorders
• Known sucrase insufficiency, isomaltase insufficiency, fructose intolerance, glucose malabsorption, galactose malabsorption, galactose intolerance or Lapp-lactase deficiency
• History of pulmonary embolism or deep venous thrombosis
• Major surgery less than or equal to 2 weeks prior to enrollment or any planned surgery within treatment period
• Active post-operative complication, e.g. infection, delayed wound healing
• History of hypersensitivity to sirolimus or to drugs of similar chemical classes
• Regular NSAID use (defined as more than twice a week for 4 consecutive weeks) within 3 months prior to baseline
• Use of other FAP directed drug therapies (accepted if discontinued 3 months prior to start of the study)
• Subjects requiring systemic anticoagulation
• Co-medication that could interact with sirolimus
• Abnormal laboratory results (assessed within 14 days prior to start of study drug)