Bicalutamide + BCG for Bladder Cancer

(BicaBCa Trial)

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for non-muscle invasive bladder cancer. It compares the usual bladder cancer treatment, Bacille Calmette-Guérin (BCG), with and without an added drug called bicalutamide, a medication typically used for prostate cancer. The researchers aim to determine if adding bicalutamide enhances the treatment's effectiveness. Men advised by their doctor to begin BCG treatment for bladder cancer might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that using bicalutamide with BCG, a treatment for bladder cancer, yields promising results. Patients generally find bicalutamide safe. One study found that even frail patients or those with muscle loss tolerated bicalutamide well. However, bicalutamide is not officially approved for use with other treatments like BCG, so less safety information may be available for this combination.

While side effects can occur, many people tolerate the treatment without major issues. Discuss any concerns with a healthcare provider to understand what to expect and how to manage side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Bicalutamide with Bacille Calmette-Guérin (BCG) for treating bladder cancer because it introduces a novel approach by adding an oral anti-androgen therapy to the standard BCG treatment. Unlike current treatments, which often rely solely on BCG for immune system stimulation, Bicalutamide targets androgen receptors, potentially interfering with cancer cell growth. This dual mechanism could enhance treatment effectiveness, offering a promising new option for patients who may not respond adequately to BCG alone.

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

Research shows that bicalutamide, a type of medication, may help treat bladder cancer by encouraging cancer cells to break down and die. In this trial, some participants will receive bicalutamide alongside Bacille Calmette-Guérin (BCG) treatment. Studies have found that stopping certain hormones from working can slow the growth of bladder cancer cells. Early evidence suggests that patients using treatments like bicalutamide may experience better outcomes, including a longer period without cancer recurrence. Overall, initial findings are promising for bicalutamide as a treatment option for bladder cancer. ^{1 2 5 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6965281/

Androgen receptor antagonist bicalutamide induces ... We confirmed that the AR antagonist bicalutamide promotes autophagy and apoptosis in bladder cancer cells by upregulating the expression of ULK2.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05327647

NCT05327647 | A Phase II Trial of Bicalutamide in Patients ... This is a phase II randomized controlled clinical trial comparing standard induction BCG versus bicalutamide and standard induction BCG among patients with non ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10886823/

Roles of Androgen Receptor Signaling in Urothelial ... Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2405456920302868

Switching Cancers: A Systematic Review Assessing the ... Cell line studies suggest that AR antagonists (such as bicalutamide and enzalutamide) may directly inhibit the growth of bladder cancer cells in vitro [20], [24] ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.784627/full

Impact of Androgen Suppression Therapy on the Risk and ... Recurrence-free survival (RFS) was improved among AST users compared with nonusers (HR: 0.68, 95% CI: 0.48–0.95), while no significant difference between AST ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/020498s028lbl.pdf

CASODEX (bicalutamide) tablet, for oral use Safety Data from Clinical Studies using CASODEX 150 mg. CASODEX 150 mg is not approved for use either alone or with other treatments. Two identical multi ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.122

Outcomes, frailty status, and body composition of men with ... Bicalutamide and dutasteride was generally safe and feasible in a cohort of HSPC with increased pre-treatment frailty and sarcopenia.