Sirolimus and Familial Adenomatous Polyposis (FAP)

NCT03095703 | Completed Phase 2 Results DMC

• 1 other identifier: NL55868.018.15
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the 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.

Conditions

Adenomatous Polyposis Coli

Keywords

Sirolimus; Intestinal adenomas

Outcome Measures

Primary Outcomes (2)

• Change in Marked Polyp Size

  Effect of sirolimus on the size of 5 marked polyps per patient based on video observations.

  6 Months

• Median Number of Treatment-Related Adverse Events Per Participant

  Summary analysis of adverse events, clinical laboratory abnormalities and regular physical examination.

  6 Months

Secondary Outcomes (2)

• Median Difference in Number of Intestinal Polyps

  6 Months

• Global Polyp Burden

  6 Months

Study Arms (1)

Sirolimus

EXPERIMENTAL

All patients will receive sirolimus for the duration of the study, with a trough level target range of 5-8 ng/ml.

Drug: Sirolimus

Interventions

Sirolimus DRUG

Participants will be given sirolimus tablets. The starting dose is 2 mg once daily which will be given in 1mg tablets. On day 7 the first trough level is measured (using the LC-MS/MS method) and if not within the target range of 5-8ng/ml, dosing adjustments are made. In case of dosing adjustments, the next trough level is measured seven days later and this is repeated weekly until the target range is achieved. In case trough levels are within the target range, the next trough level measurement is at month 3, after which dosing adjustments are made if necessary, and at month 6. The maximum daily dose is 40mg. No placebo is given.

Also known as: Rapamune

Sirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Centre

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Related Publications (1)

• Roos VH, Meijer BJ, Kallenberg FGJ, Bastiaansen BAJ, Koens L, Bemelman FJ, Bossuyt PMM, Heijmans J, van den Brink G, Dekker E. Sirolimus for the treatment of polyposis of the rectal remnant and ileal pouch in four patients with familial adenomatous polyposis: a pilot study. BMJ Open Gastroenterol. 2020 Dec;7(1):e000497. doi: 10.1136/bmjgast-2020-000497.

  PMID: 33376109 DERIVED

MeSH Terms

Conditions

Adenomatous Polyposis Coli

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Adenomatous Polyps; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Prof. dr. Evelien Dekker
• Organization: Amsterdam UMC, location Academic Medical Center

e.dekker@amsterdamumc.nl

+3120-5663534

Study Officials

• Evelien Dekker, MD, PhD

  Academic Medical Centre Amsterdam

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor MD

Model Details: A Prospective phase II pilot study with 5 patients with a follow-up of 6 months.

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 30, 2017
• Study Start: October 3, 2017
• Primary Completion: December 10, 2018
• Study Completion: December 10, 2018
• Last Updated: October 24, 2024
• Results First Posted: October 24, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)