Familial adenomatous polyposis
Conditions
Interventions
Trade Name: Rapamune
Pharmaceutical Form: Tablet
Sponsors
None listed
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - = 18 years -A genetically confirmed APC mutation -Classical FAP phenotype (100-1000 colorectal adenomatous polyps) -Subtotal colectomy with ileorectal anastomosis (IRA) or ileo-anal pouch anastomosis -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 treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -Inability to give informed consent -Participation in another interventional clinical trial -Subjects who are pregnant or breast-feeding -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 -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 -Use of other FAP directed drug therapies -Subjects requiring systemic anticoagulation -Co-medication that could interact with sirolimus -Significant abnormalities in hepatic function -Significant hematologic abnormalities -Increased fasting serum cholesterol or triglyceride (whether or not on lipid-lowering therapy) -Increased glucose (venous, fasting): >6.4 mmol/L -Electrolyte abnormalities -Calculated glomerular filtration rate (GFR) less than 40 mL/min/1.73m2 using the simplified Modification of Diet in Renal Disease (MDRD) formula -Spot urine protein to creatinine ratio (UPr/Cr) greater than or equal to 0.5
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 6 Months;Main Objective: The aim of our study is to investigate the effect of sirolimus on the progression of intestinal adenomas in patients with FAP and to assess the safety of this treatment;Secondary Objective: Not applicable; Primary end point(s): • Size of 5 marked polyps 5 patients with FAP and a large intestinal polyp burden • Safety outcomes reported by summary analysis of adverse events , clinical laboratory abnormalities and regular physical examination | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Number of polyps • Global polyp burden • Histology (tubular, tubulovillous or villous histology and degree of dysplasia) • Patient reported quality of life using HRQoL questionnaires • Rate of cell proliferation in healthy intestinal mucosa and adenomatous tissue • Immunohistochemistry of mTOR targets (such as eEF2 kinase, phospho-S6) in healthy intestinal mucosa and adenomatous tissue ;Timepoint(s) of evaluation of this end point: 6 Months | — |
Countries
Netherlands
Outcome results
None listed