Verity-BCG for Bladder Cancer

(EVER Trial)

Recruiting at 5 trial locations

Overseen By Jalees Farhan

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Verity Pharmaceuticals Inc.

Must not be taking: Steroids, Chemotherapy, Biologics, others

Disqualifiers: Urothelial carcinoma, HIV, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the effectiveness of a new bladder cancer treatment, Verity-BCG (a type of immunotherapy), with the standard treatment, OncoTICE, in preventing cancer recurrence over two years. It targets individuals with intermediate to high-risk non-muscle-invasive bladder cancer who have not previously received BCG treatment. Those diagnosed with bladder cancer within the last 60 days and who have had all visible cancer surgically removed may be suitable candidates. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those currently on certain cancer treatments or steroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that Verity-BCG, a treatment for bladder cancer, is as safe as other similar treatments. Research indicates no major safety differences between the Russian strain and other BCG strains. In a study with 123 bladder cancer patients, 95.9% experienced some side effects from BCG treatment, but serious reactions were rare.

OncoTICE, another BCG treatment, serves as a standard option for bladder cancer. Its safety is well-documented, and it is generally considered safe for patients.

Both Verity-BCG and OncoTICE are administered directly into the bladder, so side effects typically occur in the bladder area, such as irritation or discomfort, rather than affecting the whole body. While side effects are common with BCG treatments, they are often mild. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Verity-BCG for bladder cancer because it uses the Russian BCG-I strain, which is different from the TICE strain found in the standard OncoTICE treatment. This unique strain could potentially offer better immune response or different efficacy in treating bladder cancer. Since both treatments involve a freeze-dried powder for bladder instillation, the key distinction lies in the specific strain of Bacillus Calmette-Guérin (BCG) used, which might lead to improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

This trial will compare Verity-BCG with OncoTICE for treating non-muscle-invasive bladder cancer (NMIBC). Research has shown that Verity-BCG, which uses a specific type of BCG vaccine from Russia, effectively treats NMIBC. Studies indicate that this vaccine performs as well as other BCG types, helping patients avoid cancer recurrence and progression. Additionally, research has found that the safety profile of this vaccine is similar to other BCG treatments, with no major differences in efficacy or safety. Therefore, strong evidence supports the effectiveness of Verity-BCG for treating bladder cancer. ^{1 3 4 5 6}

Who Is on the Research Team?

Girish S Kulkarni, MD

Principal Investigator

Princess Margaret Cancer Centre, 700 University Ave, 6-824 Toronto, ON, M5G 1X6, Canada

Alexandre R Zlotta, MD, PhD, FRCSC

Principal Investigator

Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5

Are You a Good Fit for This Trial?

This trial is for adults with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC) who have never been treated with BCG therapy, except for childhood tuberculosis vaccination. Participants must have had a complete resection of the tumor and show no signs of metastatic disease.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

I agree to use contraception or remain abstinent.

My bladder cancer was surgically removed and confirmed by a lab within the last 60 days.

Exclusion Criteria

My condition is limited to the surface layer of the bladder.

My cancer is either squamous cell or adenocarcinoma.

I have received BCG therapy, not including childhood TB vaccination.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravesical instillation of either Verity-BCG or OncoTICE for bladder cancer management

24 months

Follow-up

Participants are monitored for recurrence-free survival and quality of life

12 months

Long-term Follow-up

Participants are monitored for overall survival, progression-free survival, and safety outcomes

36 months

What Are the Treatments Tested in This Trial?

Interventions

• OncoTICE
• Verity-BCG

Trial Overview The study tests Verity-BCG against the standard OncoTICE BCG strain in preventing cancer recurrence over 24 months in NMIBC patients. It aims to determine if Verity-BCG is at least as effective as OncoTICE.

How Is the Trial Designed?

Group I: Verity-BCG Experimental Treatment 1 Intervention

* Bacillus Calmette-Guérin (BCG): Strain Russian BCG-I * Freeze-dried powder for bladder instillation

Group II: OncoTICE Active Control 1 Intervention

* Standard of Care * Bacillus Calmette-Guérin (BCG): Strain TICE * Freeze-dried powder for bladder instillation

Who Is Running the Clinical Trial?

Verity Pharmaceuticals Inc.

Lead Sponsor

Trials

2

Recruited

660+

Published Research Related to This Trial

This study aims to systematically evaluate the efficacy and safety of Bacillus Calmette-Guerin (BCG) treatment for bladder cancer by reviewing high-quality trials from various databases, ensuring a comprehensive analysis.

The findings will provide crucial evidence to determine the effectiveness of BCG in treating bladder cancer, potentially influencing treatment decisions for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. Zhang, ZH., Yin, L., Zhang, LL., et al.[2023]

Intravesical BCG therapy has been effective in improving survival rates for bladder cancer, but a global shortage of the standard OncoTice strain has led to the use of alternative strains.

A case report highlights a severe complication, granulomatous epididymo-orchitis, in an 82-year-old man treated with the alternative SII Onco BCG strain, indicating potential risks associated with using non-standard BCG strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A severe complication of intravesical bacillus Calmette-Guerin: An effect of different strains. Low, LS., Scholtz, D., Leyland, J., et al.[2021]

In a study of 123 patients receiving intravesical BCG treatment for bladder cancer, 95.9% experienced adverse drug reactions, but serious reactions leading to discontinuation were rare, indicating that BCG instillation is generally well tolerated.

The necessity for treatment of adverse effects was significantly influenced by the purpose of the instillation and the BCG dose, suggesting that closer monitoring may be required for patients receiving higher doses (80 mg) for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of intravesical bacillus Calmette-Guerin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder. Koga, H., Kuroda, M., Kudo, S., et al.[2006]

In a systematic review of 1901 patients with medium- to high-risk bladder cancer, intravesical BCG was found to significantly reduce tumor recurrence compared to mitomycin C, particularly in high-risk patients, with a highly significant result (P < 0.001).

There were no significant differences between mitomycin C and BCG regarding disease progression or overall survival, suggesting that while BCG may be more effective for recurrence, both treatments have similar long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical bacillus Calmette-Guérin is superior to mitomycin C in reducing tumour recurrence in high-risk superficial bladder cancer: a meta-analysis of randomized trials. Shelley, MD., Wilt, TJ., Court, J., et al.[2022]

The OncuriaTM test, which analyzes 10 cancer-associated biomarkers in urine, was able to predict the effectiveness of intravesical BCG treatment in 64 patients with intermediate or high-risk non-muscle-invasive bladder cancer, achieving a high accuracy (AUROC 0.89).

Patients with elevated levels of specific biomarkers (ANG, CA9, and MMP10) in their urine were found to have a significantly higher risk of disease recurrence, suggesting that monitoring these levels could help identify patients who may not respond well to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of a multiplex urinalysis test for the prediction of intravesical BCG treatment response: A pilot study. Murakami, K., Kamat, AM., Dai, Y., et al.[2023]

In a study of 160 patients with high-risk non-muscle-invasive bladder cancer (NMIBC), both Tice and Connaught strains of Bacillus Calmette-Guérin (BCG) showed comparable rates of recurrence-free survival (RFS) and progression-free survival (PFS) after treatment, indicating that Tice can be a viable alternative during the Connaught strain shortage.

However, Tice was associated with a significantly higher risk of disease progression (HR = 5.30), suggesting that while it is effective, patients receiving Tice may need closer monitoring for potential cancer advancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison of different BCG strains in the intravesical treatment of non-muscle invasive urothelial carcinoma of urinary bladder-A real-world practice. Chen, YK., Huang, EY., Chang, YH., et al.[2023]

Intravesical BCG treatment for bladder cancer is generally safe and effective, but it can lead to rare but serious complications, such as a mycotic abdominal aortic aneurysm, as seen in a 77-year-old patient 18 months after treatment.

The exact mechanism of action for BCG is unclear, and while it typically causes localized inflammation, there is a need for updated screening methods and more research on the long-term risks and management of vascular complications associated with BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aorto-enteric fistula development secondary to mycotic abdominal aortic aneurysm following intravesical bacillus Calmette-Guerin (BCG) treatment for transitional cell carcinoma of the bladder. Roylance, A., Mosley, J., Jameel, M., et al.[2021]

In a study of 165 patients with highest-risk non-muscle-invasive bladder cancer treated with intravesical bacillus Calmette-Guérin (BCG), 30% experienced recurrence and 14% progressed to muscle-invasive disease over a median follow-up of 53 months, indicating that BCG can effectively manage this high-risk group.

Carcinoma in situ in the prostatic urethra was identified as a significant predictor of both recurrence and progression in the highest-risk patients, suggesting that specific risk factors should be considered when evaluating treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes after intravesical bacillus Calmette-Guérin for the highest-risk non-muscle-invasive bladder cancer newly defined in the Japanese Urological Association Guidelines 2019. Miyamoto, T., Miyake, M., Toyoshima, Y., et al.[2021]

In a study of 114 patients with non-muscle invasive bladder cancer, the BCG Danish 1331 strain showed a significantly lower incidence of moderate to severe adverse events compared to the BCG Moscow-I strain, indicating it may be a safer option for treatment.

Both strains demonstrated similar efficacy in terms of 3-year recurrence-free survival (80.0% for Danish 1331 vs. 72.9% for Moscow-I) and progression-free survival (96.5% for Danish 1331 vs. 97.8% for Moscow-I), suggesting that while safety profiles differ, their effectiveness in preventing cancer recurrence is comparable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravesical bacillus Calmette-Guerin (BCG) in treating non-muscle invasive bladder cancer-analysis of adverse effects and effectiveness of two strains of BCG (Danish 1331 and Moscow-I). Thyavihally, YB., Dev, P., Waigankar, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11286194/

Efficacy and tolerability of bacillus Calmette-Guérin strain ... CONCLUSIONS. BCG Russia was well-tolerated and resulted in comparable RFS and PFS to historical results of prospective clinical trials with other BCG strains. ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05037279

NCT05037279 | Evaluating Safety and Efficacy of Verity- ... The aim of this study is to evaluate the effect of Verity-BCG in patients with intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) and to ...

3. bjui-journals.onlinelibrary.wiley.com bjui-journals.onlinelibrary.wiley.com/doi/10.1002/bco2.70034

Real‐world oncological and toxicity outcomes with the ... This study aims to determine the oncological effectiveness and adverse-effect profile of the Moscow strain of intravesical bacille Calmette– ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143925003497

A randomized prospective trial comparing Bacillus ... This randomized prospective study found no statistically significant differences in efficacy or safety between the BCG RIVM and Russian ...

5. withpower.com withpower.com/trial/phase-3-carcinoma-transitional-cell-2022-cca99

Verity-BCG for Bladder Cancer (EVER Trial) In a study of 123 patients receiving intravesical BCG treatment for bladder cancer, 95.9% experienced adverse drug reactions, but serious reactions leading to ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41006133/

A randomized prospective trial comparing Bacillus ... Conclusions: BCG RIVM and Russian substrains demonstrated comparable efficacy and safety, supporting substrain selection based on availability ...