Bicalutamide + BCG for Bladder Cancer

(BicaBCa Trial)

Recruiting at 7 trial locations

Overseen By Paul Toren, MD,PhD,FRCSC

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: CHU de Quebec-Universite Laval

Must be taking: Intravesical BCG

Must not be taking: Coumadin, Investigational drugs

Disqualifiers: Myocardial infarction, Heart failure, Hypertension, Liver disease, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II randomized controlled clinical trial comparing standard induction BCG versus bicalutamide and standard induction BCG among patients with non-muscle invasive bladder cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on certain treatments like coumadin or investigational drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Bicalutamide + BCG for bladder cancer?

Research shows that Bacillus Calmette-Guérin (BCG) can help reduce the progression of bladder cancer, although it may have high side effects. This suggests that BCG is effective in treating bladder cancer, which is part of the treatment being studied. ^{1 2 3 4 5}

Is the combination of Bicalutamide and BCG safe for humans?

BCG treatment for bladder cancer is generally safe, with only minor side effects reported. Rarely, it can cause arthritis (joint inflammation), which usually responds well to anti-inflammatory medications. ^{2 4 6 7 8}

What makes the Bicalutamide + BCG treatment unique for bladder cancer?

The Bicalutamide + BCG treatment is unique because it combines BCG, a vaccine originally used to prevent tuberculosis, with Bicalutamide, a drug typically used for prostate cancer, to enhance the immune response against bladder cancer. BCG is already a well-established treatment for non-muscle invasive bladder cancer, known for its ability to prevent tumor recurrence and progression by stimulating the immune system. ^{2 6 9 10 11}

Research Team

Girish Kulkarni, BSc, MD, PhD, FRCSC

Principal Investigator

The Princess Margaret Cancer Foundation

Wassim Kassouf, MDCM,FRCSC

Principal Investigator

McGill University Health Centre/Research Institute of the McGill University Health Centre

Paul Toren, MD,PhD,FRCSC

Principal Investigator

CHU de Québec-Université Laval

Jean-Baptiste Lattouf, MD,FRCSC

Principal Investigator

Centre Hospitalier Universitaire de Montréal (CHUM)

Melissa Huynh, MD,MPH,FRCSC

Principal Investigator

London Health Sciences Centre, Victoria Hospital

Eligibility Criteria

This trial is for male patients over 18 with non-muscle invasive bladder cancer who are set to receive BCG treatment. They must not have had BCG or certain chemotherapy within the last 5 years, no recent severe heart issues, thromboembolism, significant liver/kidney disease, neutropenia, hypogonadism or prostate cancer treatments (unless stable for >5 years). Participants with reproductive partners must use two birth control methods during and for 3 months post-trial.

Inclusion Criteria

I am a man aged 18 or older.

My urologist has recommended BCG treatment for me.

I received gemcitabine, epirubicin, or mitomycin C right after surgery.

Exclusion Criteria

My liver tests are more than twice the normal limit.

I have not had a heart attack or been hospitalized for heart failure in the last year.

Patients taking an investigational drug within 3 weeks of enrollment into this study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily intake of 150 mg bicalutamide or placebo for 3 months, overlapping with 6 cycles of intravesical instillations of BCG

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

33 months

Treatment Details

Interventions

• Bicalutamide
• Control Arm

Trial Overview The study compares standard induction Bacillus Calmette-Guérin (BCG) therapy alone versus combined with bicalutamide in treating bladder cancer. It's a phase II trial where participants are randomly assigned to either continue only with their scheduled BCG treatment or to take bicalutamide alongside it.

Participant Groups

Group I: Bicalutamide Experimental Treatment 1 Intervention

Induction intravesical Bacille Calmette-Guérin treatment with 150 mg daily oral bicalutamide for 90 days (in cohort A and cohort B)

Group II: Control Arm Active Control 1 Intervention

cohort A: Induction intravesical Bacille Calmette-Guérin treatment cohort B: Induction intravesical Bacille Calmette-Guérin treatment with 150 mg daily oral placebo for 90 days

Control Arm is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as TICE BCG for:

• Bladder cancer

Approved in United States as TheraCys BCG for:

• Bladder cancer

Approved in European Union as OncoTICE for:

• Bladder cancer

Approved in Canada as ImmuCyst for:

• Bladder cancer

Approved in Japan as BCG Vaccine for:

• Bladder cancer
• Tuberculosis

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Cancer Research Society

Collaborator

Trials

8

Recruited

5,400+

Cancer Research Society

Collaborator

Trials

6

Recruited

650+

Findings from Research

In a study of 563 patients with non-muscle-invasive bladder cancer (NMIBC), using one-third-dose (1/3D) bacillus Calmette-Guérin (BCG) did not negatively impact time to cancer recurrence or progression compared to full-dose (FD) BCG.

Cancer-specific survival rates were similar between patients receiving 1/3D and FD BCG, suggesting that 1/3D BCG is a safe and effective alternative, especially during BCG shortages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced-dose bacillus Calmette-Guérin (BCG) in an era of BCG shortage: real-world experience from a tertiary cancer centre. Lobo, N., Bree, KK., Hensley, PJ., 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]

A modified 3-year BCG maintenance therapy following a 6-week induction did not significantly reduce recurrence or progression rates of high-risk non-muscle-invasive bladder carcinoma compared to induction therapy alone, with similar disease-free intervals and time to progression.

The modified regimen exhibited a low toxicity profile, with fewer patients discontinuing treatment due to side effects, although common local side effects included urinary frequency and dysuria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013. Martínez-Piñeiro, L., Portillo, JA., Fernández, JM., et al.[2015]

In a study of 219 patients with high-grade T1 non-muscle-invasive bladder cancer, using a half-dose of the BCG Moreau strain (40 mg) showed similar rates of recurrence, progression, and cancer-specific mortality compared to the standard dose (80 mg) over a median follow-up of 74.6 months.

The half-dose BCG treatment had a low complication rate, with only 0.9% experiencing treatment intolerance, suggesting it could be a safe and effective alternative amid BCG shortages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moreau Strain Bacillus Calmette-Guérin Low Versus Standard Dose in the Treatment of High-Grade T1 Bladder Cancer: A Retrospective Observational Cohort Study. Carneiro, BDB., Sanches, BCF., Andrade, DL., et al.[2020]

In a study of 333 high-risk non-muscle-invasive bladder cancer patients, those who experienced Bacillus Calmette-Guerin (BCG) shortages had a significantly lower 3-year recurrence-free survival rate (38.0%) compared to those who did not experience shortages (60.2%).

The analysis revealed that BCG shortage was an independent risk factor for bladder cancer recurrence, with a hazard ratio of 1.55, indicating that patients affected by the shortage are more likely to experience a recurrence of their cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Bacillus Calmette-Guerin shortages with bladder cancer recurrence: A single-center retrospective study. Lee, S., Lim, B., You, D., et al.[2021]

Infantile BCG vaccination is associated with a 35-37% lower incidence of bladder cancer later in life, based on preliminary data analysis of various factors including gender and socio-economic status.

Despite the promising findings, there is limited existing literature on the relationship between BCG vaccination and bladder cancer incidence, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis. Trigo, S., Gonzalez, K., Di Matteo, L., et al.[2021]

The Bacillus Calmette-Guérin (BCG) vaccine is primarily used safely for treating superficial bladder cancer through intravesical administration, with only minor side effects reported.

Although rare, cases of arthritis following BCG therapy have been documented, but they typically respond well to non-steroidal anti-inflammatory drugs (NSAIDs).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCG immunotherapy--from pathophysiology to clinical practice. Tishler, M., Shoenfeld, Y.[2019]

The BCG vaccine has shown efficacy in treating non-muscle invasive bladder cancer, suggesting it can be an effective immunotherapy option for this type of cancer.

The study discusses potential strategies to enhance the effectiveness of the BCG vaccine, including the use of low doses and approaches to overcome resistance in bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IMMUNOTHERAPY OF BLADDER CANCER. BCG VACCINE: PRINCIPLES OF ACTION, EFFICACY AND SAFETY. Glybochko, PV., Fisenko, VP.[2018]

Vaccination with a mixture of BCG and MBT-2 cells in mice led to significant immunological protection, as the vaccinated mice rejected MBT-2 cells that had been cocultured with BCG, indicating a strong immune response.

The study demonstrated that the immune system of vaccinated mice was specifically activated against MBT-2 cells, showing cytocidal activity, which suggests that this vaccination strategy could be effective in preventing bladder tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological protection induced by bacillus Calmette-Guérin treatment in a murine bladder tumor model. Iwasaki, A., Kawai, K., Hayashi, H., et al.[2019]

Mycobacterium brumae has been found to be more effective than Bacillus Calmette-Guérin (BCG) in inhibiting the growth of low-grade bladder cancer cells and shows similar effects against high-grade cells, indicating its potential as a superior treatment option.

Unlike BCG, M. brumae does not persist in the body, which reduces the risk of infections, and it also enhances the immune response against bladder cancer, leading to prolonged survival in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonpathogenic Mycobacterium brumae Inhibits Bladder Cancer Growth In Vitro, Ex Vivo, and In Vivo. Noguera-Ortega, E., Secanella-Fandos, S., Eraña, H., et al.[2022]

BCG vaccine, originally developed for tuberculosis, has proven to be an effective immunotherapy for aggressive localized bladder cancer, significantly reducing tumor recurrence when administered through six weekly intravesical instillations after tumor resection.

A maintenance schedule of three additional treatments at 3, 6, 12, 18, 24, 30, and 36 months after initial treatment has been shown to further decrease disease progression and mortality, highlighting the importance of sustained immune stimulation in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCG success story: From prevention of tuberculosis to optimal bladder cancer treatment. Lamm, DL., Morales, A.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Reduced-dose bacillus Calmette-Guérin (BCG) in an era of BCG shortage: real-world experience from a tertiary cancer centre. [2022]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013. [2015]

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

Moreau Strain Bacillus Calmette-Guérin Low Versus Standard Dose in the Treatment of High-Grade T1 Bladder Cancer: A Retrospective Observational Cohort Study. [2020]

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

Association of Bacillus Calmette-Guerin shortages with bladder cancer recurrence: A single-center retrospective study. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

BCG immunotherapy--from pathophysiology to clinical practice. [2019]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

IMMUNOTHERAPY OF BLADDER CANCER. BCG VACCINE: PRINCIPLES OF ACTION, EFFICACY AND SAFETY. [2018]

9. Australia pubmed.ncbi.nlm.nih.gov

Immunological protection induced by bacillus Calmette-Guérin treatment in a murine bladder tumor model. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Nonpathogenic Mycobacterium brumae Inhibits Bladder Cancer Growth In Vitro, Ex Vivo, and In Vivo. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

A BCG success story: From prevention of tuberculosis to optimal bladder cancer treatment. [2022]