eRapa for Adenomatous Polyposis

Recruiting at 9 trial locations

Overseen By Nancy Gady

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rapamycin Holdings Inc.

Must not be taking: NSAIDs, Immunosuppressants

Disqualifiers: Recent colectomy, High grade dysplasia, Cancer, Pregnancy, Immunosuppressed, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 months

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests Encapsulated Rapamycin (eRapa) taken by mouth to help patients with Familial Adenomatous Polyposis (FAP) reduce the number of polyps in their colon. The medication works by slowing down cell growth, aiming to manage this genetic condition more effectively. Rapamycin has shown potential in early research for preventing the development of polyps in FAP.

Do I need to stop my current medications to join the trial?

The trial requires a 4-week washout period for any FAP-directed drug therapy, including NSAIDs, except for aspirin. You can continue taking up to 81 mg of aspirin a day or 650 mg per week. Other medications that significantly alter rapamycin metabolism are not allowed.

Will I have to stop taking my current medications?

The trial requires participants to stop taking non-steroidal anti-inflammatory drugs (NSAIDs) other than aspirin during the study. If you are on other FAP-directed drug therapy, you must complete a 4-week period without these medications before enrolling.

What data supports the idea that eRapa for Adenomatous Polyposis is an effective drug?

The available research shows that eRapa, a form of rapamycin, significantly improved the survival of mice with a condition similar to Adenomatous Polyposis. These mice lived longer than expected, even compared to normal mice, without harmful effects on their immune system. This suggests that eRapa could be a promising option for preventing cancer in people with this condition, potentially reducing the need for surgery. ^{1 2 3 4 5}

What data supports the effectiveness of the drug eRapa for adenomatous polyposis?

Research on mice with a genetic condition similar to adenomatous polyposis showed that eRapa, a form of rapamycin, improved their survival and extended their lifespan. This suggests that eRapa could potentially help prevent cancer in people with similar conditions without harming the immune system. ^{1 2 3 4 5}

What safety data exists for eRapa treatment?

The safety data for eRapa, also known as Encapsulated Rapamycin, has been evaluated in various contexts. A Phase I trial in prostate cancer patients showed that eRapa was safe and well-tolerated, with some low-grade toxicities and transient worsening of quality of life, particularly with daily dosing. Weekly dosing was better tolerated and impacted immune response positively. In a mouse model of familial adenomatous polyposis (FAP), eRapa improved survival without causing detrimental immune effects, suggesting it could be a safe cancer preventative. Additionally, mTOR inhibitors like sirolimus, which eRapa is based on, have known adverse events such as stomatitis, wound-healing complications, and metabolic issues, but these can be managed with careful monitoring. ^{1 2 3 6 7}

Is eRapa safe for human use?

eRapa has been tested in a small study with prostate cancer patients and was found to be generally safe and well-tolerated. Some patients experienced mild side effects like fatigue and changes in immune cells, but these effects were temporary and resolved after stopping the treatment. Additionally, mTOR inhibitors like rapamycin have been used safely in other medical conditions, with most side effects being manageable with proper monitoring. ^{1 2 3 6 7}

Is the drug eRapa a promising treatment for Adenomatous Polyposis?

Yes, eRapa is a promising drug for Adenomatous Polyposis. It has shown potential in extending the lifespan of mice with a similar condition by preventing cancer development without harming the immune system. This suggests it could reduce the need for surgery in people with this condition. ^{1 2 6 8 9}

What makes the drug eRapa unique for treating adenomatous polyposis?

eRapa is unique because it is an enterically targeted formulation of rapamycin that can extend lifespan and prevent cancer in mouse models without suppressing the immune system, potentially reducing the need for surgery in people with familial adenomatous polyposis (FAP). ^{1 2 6 8 9}

Research Team

George E Peoples, MD

Principal Investigator

Sponsor CMO

Eligibility Criteria

This trial is for adults over 18 with Familial Adenomatous Polyposis (FAP), who have at least 10 polyps and can undergo endoscopy. They must be able to take oral medication, follow the study plan, and not breastfeed or donate eggs. Women should use effective birth control during the study and for 12 weeks after.

Inclusion Criteria

A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of eRapa administration.

I have FAP with more than 10 polyps or a family history of it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Encapsulated Rapamycin (eRapa) at one of three escalating doses/schedules for 12 months to reduce polyp burden

12 months

Endoscopy at baseline, 6 months, and 12 months

Food Effect Evaluation

Subjects undergo evaluation under fed and fasted states to determine the food effect on eRapa absorption

2 months

Randomized into fed and fasted states with a 2-week washout period

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Encapsulated Rapamycin (eRapa)

Trial Overview The trial tests Encapsulated Rapamycin (eRapa) in three different doses/schedules over a year on patients with FAP under surveillance to see if it reduces the number of polyps in their large intestine.

Participant Groups

Group I: Food Effect Experimental Treatment 1 Intervention

Upon identification of the RP2D, after a 2 week washout (14 days), subjects will be randomized into a fed and fasted (2 weeks - 14 days) two period cross over, with an intervening 2 week washout (14 days) for a total of 2 months (8 weeks).

Group II: Cohort 3 Experimental Treatment 1 Intervention

Cohort 3 will receive 0.5 mg of eRapa daily.

Group III: Cohort 2 Experimental Treatment 1 Intervention

Cohort 2 will receive 0.5mg of eRapa daily with 7 days on therapy, followed by 7 days off therapy.

Group IV: Cohort 1 Experimental Treatment 1 Intervention

Cohort 1 will receive 0.5mg of eRapa every other day.

Encapsulated Rapamycin (eRapa) is already approved in United States, European Union for the following indications:

Approved in United States as Rapamune for:

• Organ rejection in renal transplantation

Approved in European Union as Rapamune for:

• Organ rejection in renal transplantation

Who Is Running the Clinical Trial?

Rapamycin Holdings Inc.

Lead Sponsor

Trials

1

Recruited

30+

Rapamycin Holdings, Inc. dba Emtora Biosciences

Lead Sponsor

Trials

3

Recruited

210+

Biodexa Pharmaceuticals

Industry Sponsor

Trials

2

Recruited

30+

Cancer Insight, LLC dba Lumabridge

Collaborator

Trials

1

Recruited

30+

LumaBridge

Collaborator

Trials

6

Recruited

410+

Cancer Insight, LLC

Industry Sponsor

Trials

10

Recruited

520+

Findings from Research

The phase I trial of encapsulated rapamycin (eRapa) in 14 patients with low-grade prostate cancer showed that the treatment was safe and well-tolerated, with only mild adverse events reported, particularly in the daily dosing cohort.

No disease progression was observed during the study, suggesting that eRapa may have potential as a treatment to delay the progression of low-grade prostate cancer, which is a significant unmet medical need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression. Kemp Bohan, PM., Chick, RC., O'Shea, AE., et al.[2022]

Enterically targeted rapamycin (eRapa) significantly improved the survival of Apc(Min/+) mice, with most living beyond the median lifespan of wild-type mice, indicating its potential as a cancer preventative in familial adenomatous polyposis (FAP).

Chronic treatment with eRapa did not negatively impact the immune system in mouse models, suggesting that it could be a safe long-term option for preventing cancer in FAP patients, potentially reducing the need for surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

eRapa restores a normal life span in a FAP mouse model. Hasty, P., Livi, CB., Dodds, SG., et al.[2021]

Familial adenomatous polyposis (FAP) is a hereditary condition that leads to a very high risk of colorectal cancer, and while prophylactic colectomy is the standard treatment, it does not prevent other disease manifestations and carries risks of complications.

Current chemoprevention agents have not met the necessary safety and efficacy criteria, highlighting the need for new treatments; the mTOR inhibitor rapamycin shows promise based on preclinical studies, and a clinical trial is proposed to formally test its effectiveness in preventing disease progression in FAP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprevention in familial adenomatous polyposis: past, present and future. Kemp Bohan, PM., Mankaney, G., Vreeland, TJ., et al.[2022]

Rapamycin and its analogs, like everolimus, have shown strong potential in preventing cancer by targeting pre-cancerous cells and slowing down aging processes, as demonstrated in numerous mouse studies.

These drugs not only delay cancer onset in various mouse models but also show promise in organ-transplant patients, suggesting their cancer-preventive effects could be further explored in clinical trials for high-risk groups, such as smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer prevention with rapamycin. Blagosklonny, MV.[2023]

Rapamycin effectively suppressed the growth of colorectal tumors in both syngenic and xenograft mouse models, demonstrating its potential as a treatment for advanced colorectal cancer.

Combining rapamycin with standard chemotherapy drugs like 5-fluorouracil and oxaliplatin enhanced its antitumor effects without causing acute toxicity, and serum levels of TIMP-1 may serve as a useful marker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective treatment of advanced colorectal cancer by rapamycin and 5-FU/oxaliplatin monitored by TIMP-1. Wagner, M., Roh, V., Strehlen, M., et al.[2023]

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]

mTOR inhibitors, such as everolimus and sirolimus, are effective immunosuppressive agents for organ transplant recipients and cancer treatments, but they are associated with a range of adverse events (AEs) including stomatitis, wound-healing complications, and diabetes.

Most AEs related to mTOR inhibitors can be effectively managed or reversed through careful monitoring and appropriate interventions, highlighting the importance of patient selection and management strategies in optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for the management of adverse events associated with mTOR inhibitors. Kaplan, B., Qazi, Y., Wellen, JR.[2022]

Rapamycin (sirolimus) is an effective drug that inhibits the mTOR protein, which plays a crucial role in cell growth and proliferation, making it useful in treating various cancers and as an immunosuppressant.

Recent studies have shown that rapamycin can effectively manage symptoms of tuberous sclerosis, such as renal angiomyolipoma and giant cell astrocytoma, and it also improves cosmetic outcomes when applied topically for facial angiofibromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical rapamycin (sirolimus) for facial angiofibromas. Madke, B.[2021]

Chronic treatment with an enteric formulation of rapamycin (eRapa) in genetically diverse mice extended their maximum lifespan and showed potential for reducing cancer, suggesting it could be a viable pharmacological approach for humans.

The study highlights the importance of understanding the role of the mTOR pathway in both cancer and aging, and addresses misconceptions about rapamycin's immunosuppressive effects, indicating a need for safer cancer prevention strategies for the aging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?. Sharp, ZD., Curiel, TJ., Livi, CB.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

eRapa restores a normal life span in a FAP mouse model. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Chemoprevention in familial adenomatous polyposis: past, present and future. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Cancer prevention with rapamycin. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Effective treatment of advanced colorectal cancer by rapamycin and 5-FU/oxaliplatin monitored by TIMP-1. [2023]

6. Canada pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Strategies for the management of adverse events associated with mTOR inhibitors. [2022]

8. India pubmed.ncbi.nlm.nih.gov

Topical rapamycin (sirolimus) for facial angiofibromas. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?. [2021]