eRapa for Bladder Cancer Prevention

(eRapa Trial)

Recruiting at 3 trial locations

Overseen By Robert S Svatek, MD, MSC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Robert Svatek

Must not be taking: Oral glucocorticoids, Rapamycin

Disqualifiers: Muscle-invasive cancer, Active cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

166 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called eRapa (a form of the drug Rapamycin) to prevent the recurrence of non-muscle invasive bladder cancer (NMIBC). The main goal is to determine if eRapa can reduce the risk of cancer returning while also assessing its effects on immune health, brain function, and physical health without worsening overall well-being. Participants will receive either the eRapa treatment or a placebo (a pill with no active medicine) for one year. This trial suits those diagnosed with NMIBC who have had their visible tumors removed within the last 90 days. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that eRapa, a capsule form of rapamycin, is generally safe and easy to handle. In a study with prostate cancer patients, most participants taking eRapa experienced only mild side effects, such as fatigue, with no serious side effects reported. Another study tested a higher dose of rapamycin, up to 3 mg daily, in cancer patients and found it safe based on earlier data. This suggests that the 0.5 mg dose used for eRapa in current trials is likely even easier for participants to handle.

While more research is needed to confirm these findings, existing studies suggest that eRapa is a safe option for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Most treatments for bladder cancer prevention focus on traditional methods such as surgery, chemotherapy, or immunotherapy. However, eRapa is unique because it uses encapsulated rapamycin, a compound that works by targeting the mTOR pathway, a critical regulator of cell growth and proliferation. This mechanism is different from standard treatments as it potentially slows down or prevents cancer cell development at a molecular level. Researchers are excited about eRapa because it could offer a less invasive and more targeted approach, providing a preventative option that might reduce the risk of bladder cancer with fewer side effects.

What evidence suggests that eRapa might be an effective treatment for bladder cancer?

Research has shown that Rapamycin, the main ingredient in eRapa, can help prevent the progression of bladder cancer. Studies have found that Rapamycin may stop non-muscle invasive bladder cancer (NMIBC) from becoming more serious by blocking certain pathways essential for cancer cell growth. Early findings also suggest that Rapamycin might boost the immune system and improve overall physical health. In this trial, participants will be divided into two groups: one receiving eRapa and the other a placebo. While more research is needed, these early results offer hope that eRapa could be useful in preventing cancer recurrence. ^{6 7 8 9 10}

Who Is on the Research Team?

Robert S Svatek, MD, MSC

Principal Investigator

UT Health San Antonio

Are You a Good Fit for This Trial?

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 not taking oral glucocorticoids.

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

I have localized prostate cancer and am on an active surveillance program.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• eRapa
• Placebos

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.

How Is the Trial Designed?

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?

Robert Svatek

Lead Sponsor

Rapamycin Holdings, Inc. dba Emtora Biosciences

Lead Sponsor

Trials

3

Recruited

210+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. bcan.org bcan.org/clinicaltrials/trial-of-encapsulated-rapamycin-erapa-for-bladder-cancer-prevention/

Trial of Encapsulated Rapamycin (eRapa) for Bladder ... The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can improve certain ...

2. prevention.cancer.gov prevention.cancer.gov/funding-and-grants/funded-grants/R01CA252057

eRapa for bladder cancer prevention Outcome measures include efficacy, tolerability, and effects on cognition and physical function. Efficacy is assessed through standard-of-care surveillance ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04375813/trial-of-encapsulated-rapamycin-erapa-for-bladder-cancer-prevention

Trial of Encapsulated Rapamycin (eRapa) for Bladder ... The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2789170/

Intravesical delivery of Rapamycin suppresses ... In summary, these studies show that Rapamycin is highly effective for inhibition of progression from non-muscle invasive CIS to muscle invasive bladder cancer, ...

5. smartpatients.com smartpatients.com/trials/NCT04375813

Trial of Encapsulated Rapamycin (eRapa) for Bladder ... The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can improve certain ...

6. ctv.veeva.com ctv.veeva.com/study/trial-of-encapsulated-rapamycin-erapa-for-bladder-cancer-prevention

Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer ... The primary hypothesis is that eRapa decreases the risk of cancer relapse for patients with NMIBC. Secondary hypotheses are that eRapa can ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6926429/

Rapamycin prevents surgery-induced immune dysfunction in ... When this study protocol was initiated, a dose of 3 mg daily rapamycin was chosen based on safety data in surgically treated cancer patients(25) ...

8. prevention.cancer.gov prevention.cancer.gov/clinical-trials/clinical-trials-search/nct04375813

Trial of Encapsulated Rapamycin (eRapa) for Bladder Cancer ... eRapa (encapsulated rapamycin) will be investigated for secondary prevention in patients with diagnosed non-muscle invasive bladder cancer (NMIBC)

9. withpower.com withpower.com/trial/phase-3-urinary-bladder-neoplasms-2021-aa439

eRapa for Bladder Cancer Prevention 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 ...

10. biodexapharma.com biodexapharma.com/biodexa-announces-enrolment-of-first-patients-into-pivotal-phase-3-serenta-trial-in-familial-adenomatous-polyposis-fap/

Biodexa Announces Enrolment of First Patients into Pivotal ... Its Phase 2 data are promising and, if replicated in the Phase 3 Serenta trial, eRapa could become the first therapeutic treatment for FAP ...