eRapa for Bladder Cancer Prevention

Recruiting at3 trial locations

Overseen by Robert S Svatek, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Rapamycin Holdings, Inc. dba Emtora Biosciences

Must not be taking: Oral glucocorticoids, Rapamycin

Disqualifiers: Muscle-invasive cancer, Active cancer, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is evaluating whether a drug which is used to prevent organ rejection in transplant patients may also help prevent cancer from returning.

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

The trial does not specify if you need to stop taking your current medications, but you cannot be taking oral glucocorticoids when you register.

What data supports the effectiveness of the drug eRapa for preventing bladder cancer?

Research shows that Rapamycin, a component of eRapa, can effectively prevent the progression of early-stage bladder cancer to more invasive forms by inhibiting the mTOR signaling pathway, which is often active in aggressive bladder cancers. Studies in mice have demonstrated that delivering Rapamycin directly into the bladder can suppress tumor growth, suggesting potential benefits for high-risk bladder cancer patients. ^{1 2 3 4 5}

Is eRapa safe for humans?

In a study with prostate cancer patients, eRapa 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 treatment. ^{1 2 3 5 6}

How is the drug eRapa unique for bladder cancer prevention?

eRapa is unique because it targets the mTOR signaling pathway, which is involved in the progression of bladder cancer, and is delivered directly into the bladder (intravesical delivery), making it potentially more effective in preventing the progression of nonmuscle-invasive bladder cancer to invasive cancer. ^{1 2 3 5 7}

Research Team

Robert S Svatek, MD

Principal Investigator

UT Health San Antonio

Eligibility Criteria

This trial is for adults over 18 with non-muscle invasive bladder cancer diagnosed within the last 90 days. They must not be pregnant, nursing, or taking oral glucocorticoids and should agree to use contraception. Those with localized prostate cancer under surveillance may join, but those with muscle-invasive bladder cancer or other active cancers (except certain skin cancers) cannot.

Inclusion Criteria

I am 18 years old or older.

I am not taking oral glucocorticoids.

All visible tumors were removed or confirmed absent by a doctor within the last 3 months.

Exclusion Criteria

I do not have any active cancer except for skin cancer.

I am currently taking oral glucocorticoids.

I am unable to understand and agree to the study's details on my own.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either eRapa or placebo orally each weekday for one year

52 weeks

Weekly dosing (Monday-Friday)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cystoscopy every 3 months for 2 years, then every 6 months for 2 years, and at year 5

5 years

Regular cystoscopy visits

BCG Immune Therapy Maintenance

Some patients receive BCG immune therapy maintenance weekly for 6 weeks for induction, then weekly for 3 weeks at 3 months, 6 months, and every 6 months for 7 cycles

Varies per patient

Treatment Details

Interventions

• eRapa (mTOR Inhibitor)
• Placebos (Other)

Trial Overview The study tests if eRapa can prevent bladder cancer from coming back compared to a placebo. Participants will take the treatment for one year in this phase II trial where neither they nor the doctors know who's getting eRapa or placebo. The trial also looks at how eRapa affects immunity, cognition, physical function, and quality of life.

Participant Groups

Group I: Active Study Drug Group Active Control 1 Intervention

Patients will be given 0.5mg eRapa (encapuslated rapamycin) orally each weekday (Monday-Friday) for one year.

Group II: Placebo Group Placebo Group 1 Intervention

Patients will be given a placebo (visually identical to the eRapa (encapsulated rapamycin)) orally each weekday (Monday-Friday) for one year.

Who Is Running the Clinical Trial?

Rapamycin Holdings, Inc. dba Emtora Biosciences

Lead Sponsor

Trials

3

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a preclinical study using a genetically engineered mouse model, the mTOR inhibitor Rapamycin was shown to effectively prevent the progression of nonmuscle-invasive carcinoma in situ (CIS) to invasive bladder cancer.

Intravesical delivery of Rapamycin directly into the bladder was highly effective in suppressing tumor development, suggesting a promising therapeutic approach for patients at high risk of invasive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical delivery of rapamycin suppresses tumorigenesis in a mouse model of progressive bladder cancer. Seager, CM., Puzio-Kuter, AM., Patel, T., et al.[2022]

Inhibition of the mTOR pathway using rapamycin significantly decreased cell viability in bladder cancer cell lines and enhanced the effectiveness of cisplatin, a common chemotherapy drug, indicating a potential combination therapy for bladder cancer.

In mouse models, rapamycin not only prolonged survival but also improved the therapeutic effects of cisplatin, suggesting that targeting mTOR could be a promising strategy for treating urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mTOR pathway affects proliferation and chemosensitivity of urothelial carcinoma cells and is upregulated in a subset of human bladder cancers. Makhlin, I., Zhang, J., Long, CJ., et al.[2021]

In a study of 49 patients with muscle-invasive bladder cancer, the expression level of phosphorylated 4E-BP1 was found to be independently associated with recurrence-free survival, indicating its potential as a prognostic marker.

Both mTOR inhibitors, temsirolimus and Ku-0063794, effectively inhibited the growth of bladder cancer cells, but Ku-0063794 showed a greater reduction in p-4E-BP1 levels, suggesting that targeting this pathway may offer a promising treatment strategy for muscle-invasive bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of 4E-binding protein 1 as a therapeutic target for invasive urothelial carcinoma of the bladder. Nishikawa, M., Miyake, H., Behnsawy, HM., et al.[2021]

Rapamycin effectively delayed the proliferation of human transitional cell carcinoma cell lines without inducing apoptosis, suggesting it may cause cell cycle arrest.

The study found that rapamycin inhibited the synthesis of vascular endothelial growth factor (VEGF) under hypoxic conditions, indicating potential antiangiogenic effects that warrant further investigation in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapamycin inhibits in vitro growth and release of angiogenetic factors in human bladder cancer. Fechner, G., Classen, K., Schmidt, D., et al.[2013]

Local administration of a chemical inhibitor targeting the mammalian target of rapamycin (mTOR) significantly suppressed bladder cancer growth in a new preclinical mouse model, indicating its potential as an effective treatment.

The findings support further clinical evaluation of mTOR inhibitors for bladder cancer and suggest the possibility of exploring other molecular therapies for localized treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The molecular, the bad, and the ugly: preventing bladder cancer via mTOR inhibition. McConkey, DJ., Dinney, CP.[2021]

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]

Early administration of rapamycin significantly reduces tumor growth in a rat model of urothelial carcinoma, with 80% of rats showing no tumors when treatment started on the first day.

Delayed treatment with rapamycin, starting from the 5th week or later, leads to increased tumor growth, indicating that the timing of rapamycin administration is crucial for its anticancer efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anticancer benefits of early versus late use of rapamycin in a rat model of urothelial carcinoma. Chang, CH., Fu, YC., Li, JR., et al.[2014]

References

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

Intravesical delivery of rapamycin suppresses tumorigenesis in a mouse model of progressive bladder cancer. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The mTOR pathway affects proliferation and chemosensitivity of urothelial carcinoma cells and is upregulated in a subset of human bladder cancers. [2021]

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

Significance of 4E-binding protein 1 as a therapeutic target for invasive urothelial carcinoma of the bladder. [2021]

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

Rapamycin inhibits in vitro growth and release of angiogenetic factors in human bladder cancer. [2013]

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

The molecular, the bad, and the ugly: preventing bladder cancer via mTOR inhibition. [2021]

6. 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]

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

Anticancer benefits of early versus late use of rapamycin in a rat model of urothelial carcinoma. [2014]