BCG + Durvalumab for Bladder Cancer

(PATAPSCO Trial)

Recruiting at20 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: AstraZeneca

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of durvalumab and BCG in adults with high-risk bladder cancer who haven't had previous treatments. Durvalumab helps the immune system fight cancer, while BCG stimulates an immune response in the bladder. BCG has been used for the treatment of bladder cancer for many years and is considered very effective.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before the first dose of durvalumab, and you cannot have any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment.

What data supports the idea that BCG + Durvalumab for Bladder Cancer is an effective treatment?

The available research does not provide direct data on the effectiveness of BCG combined with Durvalumab for bladder cancer. However, it does highlight the effectiveness of BCG alone as a treatment for high-grade non-muscle-invasive bladder cancer, with a substantial cure rate in selected patients. Additionally, a study on Durvalumab alone shows promise for treating BCG-unresponsive bladder cancer. While these studies suggest that both BCG and Durvalumab have potential benefits individually, there is no specific data provided on their combined use for bladder cancer in the available research. ^{1 2 3 4 5}

What safety data is available for BCG and Durvalumab treatment in bladder cancer?

The safety data for BCG and Durvalumab treatment in bladder cancer includes studies on adverse drug reactions from BCG instillation, safety and efficacy of Durvalumab in BCG-unresponsive bladder cancer, and adverse reactions during BCG maintenance therapy. Additionally, a systematic review protocol aims to assess the safety of BCG for bladder cancer, and a Phase I trial evaluated the safety of BCG combined with pembrolizumab, which is another immune checkpoint inhibitor similar to Durvalumab. ^{1 5 6 7 8}

Is the treatment BCG and Durvalumab a promising treatment for bladder cancer?

Yes, BCG and Durvalumab show promise as a treatment for bladder cancer. BCG is a well-known treatment that helps the immune system fight cancer cells in the bladder. Durvalumab, a type of drug called an immune checkpoint inhibitor, helps the immune system attack cancer more effectively. Together, they could improve the body's ability to control and fight bladder cancer. ^{3 5 8 9 10}

Research Team

Eligibility Criteria

Adults with high-risk non-muscle-invasive bladder cancer (NMIBC) who haven't had systemic therapy for NMIBC or BCG treatment. Participants must have a life expectancy of at least 12 weeks, good organ and marrow function, and no history of immune-mediated therapy or certain autoimmune disorders. Women can't be pregnant or breastfeeding, and all participants must use effective birth control.

Inclusion Criteria

I have not had radiation treatment for bladder cancer.

I had surgery to remove all visible bladder cancer less than 4 months ago.

My bladder cancer is high-risk but hasn't spread beyond the inner layers.

Exclusion Criteria

I am not currently on any cancer treatments and do not have any uncontrolled illnesses.

My bladder cancer has spread beyond the bladder wall.

I do not have active infections like hepatitis B, C, or HIV.

Treatment Details

Interventions

• BCG (Cancer Vaccine)
• Durvalumab (PD-L1 Inhibitor)

Trial Overview The trial is testing the combination of Durvalumab (an immunotherapy drug) with BCG (a type of intravesical therapy) to see if it's safe and works well in treating adults with high-risk NMIBC who are new to this kind of treatment.

Participant Groups

Group I: Durvalumab + BCG Experimental Treatment 2 Interventions

Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.

BCG is already approved in Canada for the following indications:

Approved in Canada as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

The combination of intravesical Bacillus Calmette-Guérin (BCG) and systemic pembrolizumab was found to be safe in a phase I trial involving 18 patients with high-grade non-muscle-invasive bladder cancer, with 69% of treated patients showing no evidence of disease after 3 months.

Despite some treatment-related adverse events, including one severe case of adrenal insufficiency and several grade 3 adverse events, the overall safety profile supports further investigation, leading to the initiation of a phase III trial to evaluate the efficacy of this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment. Alanee, S., Sana, S., El-Zawahry, A., et al.[2022]

Intravesical bacillus Calmette-Guérin (BCG) therapy has shown a substantial cure rate in patients with high-grade superficial transitional cell carcinoma (TCC), indicating its efficacy as an immunotherapy for bladder cancer.

The review highlights the need to better understand the nonspecific immune modulation caused by BCG therapy, which could lead to the development of new immunotherapeutic agents for treating high-risk bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic strategies for high-risk bladder cancer. Sharma, P., Old, LJ., Allison, JP.[2018]

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 mouse model, combining lenalidomide with intravesical bacillus Calmette-Guerin (BCG) significantly reduced tumor size compared to controls, suggesting enhanced efficacy for treating high-grade non-muscle-invasive bladder cancer (NMIBC).

The combination therapy also showed increased cell death through mechanisms involving caspase-3 activation, indicating that lenalidomide may improve the effectiveness of BCG by promoting apoptosis in cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide augments the efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in vivo. Jinesh, GG., Lee, EK., Tran, J., et al.[2022]

In a phase II study involving 17 patients with BCG-unresponsive carcinoma in situ of the bladder, durvalumab showed a low complete response rate of only 12% at 6 months, indicating minimal efficacy for this condition.

The treatment was associated with some immune-related adverse events in 41% of patients, and a potential mechanism for resistance was identified through elevated complement activation genes post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder. Li, R., Sexton, WJ., Dhillon, J., et al.[2023]

In a study of 36 patients undergoing Mycobacterium bovis bacillus Calmette-Guérin (BCG) maintenance therapy for high-risk non-muscle-invasive bladder cancer, 86.7% of those who completed the therapy experienced local adverse reactions, indicating that while the therapy is common, side effects are prevalent.

The analysis suggested that severe adverse reactions, such as gross hematuria and systemic effects during the initial induction therapy, may contribute to a higher rate of discontinuation of the maintenance therapy, highlighting the importance of monitoring and managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions related to treatment compliance during BCG maintenance therapy for non-muscle-invasive bladder cancer. Miyazaki, J., Hinotsu, S., Ishizuka, N., et al.[2013]

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]

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]

Immunotherapy with Bacillus Calmette Guerin (BCG) is an effective long-term treatment for high-grade superficial bladder cancer, with a 35% recurrence rate and 74% of patients alive after a median follow-up of 71 months.

The study suggests that BCG therapy is a viable conservative option, as only 9% of patients required cystectomy, indicating that aggressive surgical intervention may not be necessary as a first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High grade superficial (G3t1) transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guerin (BCG). Pansadoro, V., Emiliozzi, P., depaula, F., et al.[2006]

The SAKK 06/19 trial is investigating a new treatment approach for muscle invasive bladder cancer (MIBC) by combining intravesical recombinant BCG with checkpoint inhibition (atezolizumab) and cisplatin-based chemotherapy, aiming for improved local and systemic disease control.

The primary goal of the trial is to achieve pathological complete remission in patients, with an interim safety analysis planned after the first 12 patients to assess any potential toxicity from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel sequential treatment strategy for patients with muscle-invasive bladder cancer (MIBC): intravesical recombinant BCG, followed by neoadjuvant chemoimmunotherapy, radical cystectomy plus pelvic lymphadenectomy and adjuvant immunotherapy - protocol of a multicentre, single arm phase 2 trial (SAKK 06/19). Petrausch, U., Spahn, M., Schneider, M., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment. [2022]

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

Immunotherapeutic strategies for high-risk bladder cancer. [2018]

3. 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]

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

Lenalidomide augments the efficacy of bacillus Calmette-Guerin (BCG) immunotherapy in vivo. [2022]

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

A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma In Situ of the Bladder. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Adverse reactions related to treatment compliance during BCG maintenance therapy for non-muscle-invasive bladder cancer. [2013]

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

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

9. England pubmed.ncbi.nlm.nih.gov

High grade superficial (G3t1) transitional cell carcinoma of the bladder treated with intravesical Bacillus Calmette-Guerin (BCG). [2006]

10. England pubmed.ncbi.nlm.nih.gov

Novel sequential treatment strategy for patients with muscle-invasive bladder cancer (MIBC): intravesical recombinant BCG, followed by neoadjuvant chemoimmunotherapy, radical cystectomy plus pelvic lymphadenectomy and adjuvant immunotherapy - protocol of a multicentre, single arm phase 2 trial (SAKK 06/19). [2023]