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

Trial Summary

What is the purpose of this trial?

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 compare our findings to the standard of care BCG formulation, OncoTICE (BCG) in order to examine our hypothesis that Verity-BCG is at least non-inferior to OncoTICE in achieving 24-month Recurrence Free Survival in NMIBC patients who are at high risk of recurrence and have never been treated with intradermal or intravesical BCG before, with the exception of tuberculosis vaccination in childhood.

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.

What data supports the effectiveness of the treatment Verity-BCG for bladder cancer?

Research shows that Bacillus Calmette-Guérin (BCG), including the OncoTICE strain, is a well-recognized treatment for high-risk non-muscle-invasive bladder cancer, effectively reducing tumor recurrence compared to other treatments like mitomycin C. ^{1 2 3 4 5}

Is Verity-BCG safe for humans?

Verity-BCG, also known as OncoTICE, is generally considered safe for treating bladder cancer, but it can cause side effects. Most side effects are mild and temporary, but rare serious complications can occur, such as issues with blood vessels. ^{1 3 6 7 8}

How is the Verity-BCG treatment for bladder cancer different from other treatments?

Verity-BCG, using the OncoTICE strain of BCG, is unique because it serves as an alternative to the Connaught strain due to global shortages, offering a different option for intravesical therapy (treatment delivered directly into the bladder) for non-muscle-invasive bladder cancer. ^{1 3 4 5 9}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

1. Netherlands 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. [2023]

2. England 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. [2022]

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

Efficacy and safety of Bacillus Calmette-Guerin for bladder cancer: A protocol of systematic review. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Application of a multiplex urinalysis test for the prediction of intravesical BCG treatment response: A pilot study. [2023]

5. Australia 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. [2021]

6. Singapore 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). [2022]

7. Australia 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. [2006]

8. Netherlands 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. [2021]

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

A severe complication of intravesical bacillus Calmette-Guerin: An effect of different strains. [2021]