Clinical trial · Interventional
Sirolimus for Cowden Syndrome With Colon Polyposis
NCT04094675CI-TRIAL-00090807completedPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Colon polyposis (the presence of multiple colon polyps) is very common with Cowden syndrome, as over 60% of patients have 50 or more polyps. In a previous clinical trial, some participants had reduction in the number of colon polyps with the use of the medication sirolimus for a very short time period. This study is investigating sirolimus and its effect on the number of colon polyps in patients with Cowden syndrome and polyposis over a 1 year period.
Conditions
Conditions (7)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Bannayan Syndrome | — | UNRESOLVED | — |
| Bannayan Zonana Syndrome | — | UNRESOLVED | — |
| Cowden Syndrome | — | UNRESOLVED | — |
| Polyposis | Polyposis | ONTOLOGY_EXACT | 0.98 |
| PTEN Gene Mutation | — | UNRESOLVED | — |
| PTEN Hamartoma Syndrome | — | UNRESOLVED | — |
| PTEN Hamartoma Tumor Syndrome | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Sirolimus | Drug | Sirolimus | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment arm
- description
- There will be a clinic visit and colonoscopy at study entrance with standard of care sampling and assessment of polyps, including resection of concerning polyps. The investigators will also collect data on well-being via the SF-36 health survey (a validated questionnaire to help monitor this aspect given anecdotal patient-level reports of improvement while on therapy). Study subjects will then begin sirolimus 2 mg by mouth daily for 1 year. Laboratories will be checked at 4 days after initiation, at 2 weeks after initiation, then every 4 weeks for 3 months, then every 3 months to complete the year of therapy Participants will have a clinic visit at 3, 6 and 9 months and include well-being assessment with the SF-36 health survey. Participants will have a clinic visit with well-being assessment and perform colonoscopy at study closure at 12 months. The investigators will perform standard of care sampling and assessment of polyps, including resection of concerning polyps.
- interventionNames
- Drug: Sirolimus
Primary outcomes (2)
- measure
- Change in colon polyp burden by number
- timeFrame
- 1 year
- description
- Assessment of change in number of colon polyps. This will be assessed for each segment of colon (ascending, transverse, descending, sigmoid, rectum) and then aggregated into a total number of colon polyps. The entrance result will be compared to the final result for each participant.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria: * Cowden syndrome or other PTEN hamartoma tumor syndrome spectrum disorder * Confirmed pathogenic or likely pathogenic PTEN germline mutation on genetic testing * Previous colonoscopy with colon polyposis. This is defined for the study as either too many polyps to remove endoscopically as judged by the performing physician at the last colonoscopy or findings indicating at least an InSIGHT stage 1 score (over 20 polyps). * Age 18 or greater * Capacity to consent to study Exclusion Criteria: * Pregnancy or plans for pregnancy while on treatment or within 3 months of stopping treatment (for both women and men) * Chronic kidney disease * Chronic renal disease * History of colon cancer or colon adenoma with high grade dysplasia * History of colectomy
References
Publications (6)
- BACKGROUNDStanich PP, Pilarski R, Rock J, Frankel WL, El-Dika S, Meyer MM. Colonic manifestations of PTEN hamartoma tumor syndrome: case series and systematic review. World J Gastroenterol. 2014 Feb 21;20(7):1833-8. doi: 10.3748/wjg.v20.i7.1833. PMID 24587660
- BACKGROUNDStanich PP, Owens VL, Sweetser S, Khambatta S, Smyrk TC, Richardson RL, Goetz MP, Patnaik MM. Colonic polyposis and neoplasia in Cowden syndrome. Mayo Clin Proc. 2011 Jun;86(6):489-92. doi: 10.4065/mcp.2010.0816. PMID 21628613
- BACKGROUNDHeald B, Mester J, Rybicki L, Orloff MS, Burke CA, Eng C. Frequent gastrointestinal polyps and colorectal adenocarcinomas in a prospective series of PTEN mutation carriers. Gastroenterology. 2010 Dec;139(6):1927-33. doi: 10.1053/j.gastro.2010.06.061. Epub 2010 Jun 27. PMID 20600018
- BACKGROUNDKomiya T, Blumenthal GM, DeChowdhury R, Fioravanti S, Ballas MS, Morris J, Hornyak TJ, Wank S, Hewitt SM, Morrow B, Memmott RM, Rajan A, Dennis PA. A Pilot Study of Sirolimus in Subjects with Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN. Oncologist. 2019 Dec;24(12):1510-e1265. doi: 10.1634/theoncologist.2019-0514. Epub 2019 Jul 26. PMID 31350329
- BACKGROUNDLynch PM, Morris JS, Wen S, Advani SM, Ross W, Chang GJ, Rodriguez-Bigas M, Raju GS, Ricciardiello L, Iwama T, Rossi BM, Pellise M, Stoffel E, Wise PE, Bertario L, Saunders B, Burt R, Belluzzi A, Ahnen D, Matsubara N, Bulow S, Jespersen N, Clark SK, Erdman SH, Markowitz AJ, Bernstein I, De Haas N, Syngal S, Moeslein G. A proposed staging system and stage-specific interventions for familial adenomatous polyposis. Gastrointest Endosc. 2016 Jul;84(1):115-125.e4. doi: 10.1016/j.gie.2015.12.029. Epub 2016 Jan 6. PMID 26769407
- DERIVEDStanich PP, Gofar K, Roberts ME, Hussan H. Sirolimus for Colon Polyposis in PTEN Hamartoma Tumor Syndrome. Clin Transl Gastroenterol. 2025 Jun 6;16(8):e00871. doi: 10.14309/ctg.0000000000000871. eCollection 2025 Aug 1.