Sirolimus for Cowden Syndrome with Colon Polyposis

Overseen By Kebire Gofar, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Disqualifiers: Pregnancy, Chronic kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the medication sirolimus (also known as Rapamune) can reduce the number of colon polyps in individuals with Cowden syndrome, a condition where over 60% of patients develop numerous colon polyps. Researchers aim to determine if taking sirolimus for one year can decrease polyps and enhance overall well-being. This trial suits those with Cowden syndrome, a specific genetic mutation (PTEN), and a previous colonoscopy indicating too many polyps for removal. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that sirolimus is likely to be safe for humans?

Research has shown that sirolimus is generally well-tolerated by people with Cowden syndrome. One study found that participants who took sirolimus for 56 days experienced improvements in skin and digestive system symptoms. However, sirolimus can cause side effects, such as changes in lab test results, increased infection risk, and lung problems.

Although sirolimus is being tested in this trial for colon polyps, it is already approved for other conditions, so doctors are familiar with its safety profile. This familiarity helps them understand its potential risks and benefits. However, since reactions can vary, monitoring each person closely during treatment is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Cowden Syndrome with colon polyposis, which often involve regular monitoring and surgical removal of polyps, sirolimus brings a fresh approach by targeting the underlying cellular mechanisms. Sirolimus works by inhibiting a protein called mTOR, which plays a key role in cell growth and proliferation. This novel mechanism could potentially slow or prevent the formation of new polyps, offering a promising alternative to frequent surgeries. Researchers are excited about sirolimus because it represents a shift from reactive to proactive management of the condition, with the potential to improve patient quality of life significantly.

What evidence suggests that sirolimus might be an effective treatment for colon polyposis in Cowden syndrome?

Research suggests that sirolimus, the treatment under study in this trial, may help reduce the number of colon polyps in people with Cowden syndrome. In earlier studies, some patients experienced a decrease in polyps after using sirolimus for a short time. Sirolimus slows the growth of certain cells, which might help reduce polyps. This medication already prevents the immune system from rejecting transplanted organs, demonstrating its potential effect on cell growth. While promising, the long-term effects and tolerance levels are still under investigation. ^{2 4 6 7 8}

Who Is on the Research Team?

Peter P. Stanich

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Cowden syndrome or related disorders, who have a genetic mutation called PTEN and more than 50 colon polyps that can't be removed endoscopically. It's not for those with chronic kidney disease, past high-grade colon tumors, colectomy history, or current/pending pregnancy.

Inclusion Criteria

I have a confirmed PTEN gene mutation.

I have Cowden syndrome or a related genetic condition.

I am able to understand and agree to participate in the study.

Exclusion Criteria

I have had colon cancer or a serious type of colon polyp.

I have long-term kidney disease.

You are pregnant, planning to become pregnant, or planning to father a child within 3 months after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sirolimus 2 mg by mouth daily for 1 year. Colonoscopy with polyp estimation at trial entrance and study completion.

52 weeks

Clinic visits at 3, 6, 9, and 12 months; Laboratories checked at 4 days, 2 weeks, then every 4 weeks for 3 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The study tests Sirolimus on patients with Cowden syndrome to see if it reduces the number of colon polyps over one year. Participants must have many polyps and a specific genetic mutation linked to their condition.

How Is the Trial Designed?

Group I: Treatment arm Experimental Treatment 1 Intervention

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.

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

PTEN Research

Collaborator

Trials

2

Recruited

60+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Sirolimus is a powerful immunosuppressant used in kidney transplantation that works by inhibiting the mTOR pathway, which is crucial for cell growth and proliferation, leading to reduced rates of acute rejection episodes to less than 10% when combined with cyclosporin A (CsA).

In clinical trials, using sirolimus at doses of 2 or 5 mg/day alongside CsA and steroids resulted in acute rejection rates of only 19% and 14% within 12 months, while also potentially reducing the need for nephrotoxic calcineurin inhibitors, although it may cause side effects like myelosuppression and increased lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a comprehensive review. Kahan, BD.[2019]

Sirolimus (rapamycin) is an effective immunosuppressant approved for preventing graft rejection in kidney transplants, with a lower risk of complications compared to other immunosuppressants.

Recent findings suggest that sirolimus may also have potential in treating skin disorders and extending lifespan, making it a promising candidate for addressing age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. Peters, T., Traboulsi, D., Tibbles, LA., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12377304/

Sirolimus for Colon Polyposis in PTEN Hamartoma Tumor ... In summary, sirolimus has promise for reduction of colorectal polyp burden in PHTS, but side effects may limit tolerance of long-term usage. Future treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04094675?term=AREA%5BConditionSearch%5D(PTEN%20Hamartoma%20Tumor%20Syndrome%20(PHTS))&rank=6

Sirolimus for Cowden Syndrome With Colon Polyposis Colon polyposis (the presence of multiple colon polyps) is very common with Cowden syndrome, as over 60% of patients have 50 or more polyps.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40478255/

Sirolimus for Colon Polyposis in PTEN Hamartoma Tumor ... Sirolimus may reduce colorectal polyps in PHTS. We designed a trial to assess the safety and impact of sirolimus on colon polyp burden in PHTS.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00971789

Sirolimus to Treat Cowden Syndrome and Other PTEN ... Experiments show that a drug called sirolimus, which is used to prevent the immune system from rejecting transplanted organs, can inhibit cancer cell growth by ...

5. nature.com nature.com/articles/pr2013246

Sirolimus treatment of severe PTEN hamartoma tumor ... Results: Sirolimus treatment improved somatic growth and reduced thymus volume. These effects diminished over the treatment period of 19 mo.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6975943/

A Pilot Study of Sirolimus in Subjects with Cowden Syndrome ... A 56‐day course of sirolimus was well tolerated in subjects with Cowden syndrome and was associated with some evidence of improvement in symptoms, skin and GI ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK1488/

PTEN Hamartoma Tumor Syndrome - GeneReviews - NCBI CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, kidney, and endometrium.

8. journals.lww.com journals.lww.com/ctg/fulltext/2025/08000/sirolimus_for_colon_polyposis_in_pten_hamartoma.12.aspx

Sirolimus for Colon Polyposis in PTEN Hamartoma Tumor... Sirolimus has the potential for significant side effects including frequent laboratory abnormalities and risk of infections and interstitial pneumonitis (12).