BCG + Durvalumab for Bladder Cancer

(PATAPSCO Trial)

Not currently recruiting at 20 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: BCG

Must not be taking: Immunosuppressants

Disqualifiers: Organ transplant, Autoimmune disorders, 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: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two treatments, BCG (a type of immunotherapy) and durvalumab (an immunotherapy drug), for individuals with high-risk non-muscle-invasive bladder cancer (NMIBC). Participants will receive this combination to determine if it manages their cancer better than current options. Ideal candidates have been diagnosed with this type of bladder cancer, have not previously received BCG treatment, and do not have cancer that has spread to muscles or other areas. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 14 days before the first dose of durvalumab.

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

Research has shown that combining Durvalumab with BCG for bladder cancer has been studied for safety. One study found that patients receiving both Durvalumab and BCG generally experienced mild or moderate side effects, such as tiredness and injection site reactions.

A large study showed positive results, indicating that adding Durvalumab to BCG treatment helped lower the risk of cancer returning or worsening. This suggests the combination can be effective and is generally well-tolerated.

Durvalumab is already approved for other conditions, indicating it has undergone safety studies before. Overall, the treatment appears safe for most people, but discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of BCG and Durvalumab for bladder cancer because it brings together two powerful treatment approaches. Unlike standard options, which typically involve either BCG alone or chemotherapy, this combination uses Durvalumab, an immune checkpoint inhibitor, to help the immune system recognize and attack cancer cells more effectively. By pairing this with BCG, which also stimulates the immune response, there's potential for a stronger, more sustained attack on the cancer. This dual approach could offer improved outcomes for patients, especially those who don't respond well to current therapies.

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

This trial will evaluate the combination of Durvalumab with BCG (Bacillus Calmette-Guérin) for bladder cancer. Research has shown that BCG alone is a well-known treatment for non-muscle-invasive bladder cancer (NMIBC). However, early findings suggest that adding Durvalumab, which boosts the immune system, might enhance the treatment's effectiveness. Initial studies of Durvalumab alone showed limited results, with only 12% of patients achieving a complete response after six months. This trial will explore whether combining it with BCG could lead to better outcomes by helping the immune system attack cancer cells more effectively. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive Durvalumab for 13 cycles every 4 weeks for a maximum of 12 months, and BCG intravesically as induction weekly for 6 weeks, followed by maintenance doses at specified intervals up to 24 months

24 months

Safety Follow-up

Participants are monitored for safety and adverse events following the completion of treatment

3 months

Long-term Follow-up

Participants are followed up for survival until 2 years from the date of treatment initiation of the last participant enrolled

42 months

What Are the Treatments Tested in This Trial?

Interventions

• BCG
• Durvalumab

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

Approved in European Union as Bacillus Calmette-Guérin for:

• Non-muscle invasive bladder cancer

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer (POTOMAC).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12065394/

A Phase 2 Study of Durvalumab for Bacillus Calmette ... Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6mo complete response of 12%. Complement activation is a ...

3. bcan.org bcan.org/clinicaltrials/phase-2-durvalumab-medi4736-for-bacillus-calmette-guerin-bcg-refactory-urothelial-carcinoma-in-situ-of-the-bladder/

Phase 2 Durvalumab (Medi4736) for Bacillus Calmette- ... The purpose of this study is to test if an experimental drug called Durvalumab (Medi4736) given by intravenous (IV) infusion is effective in treating carcinoma ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03759496

NCT03759496 | Efficacy of Durvalumab in Non-muscle- ... The investigators, therefore, propose a phase II study of intravesical administration of durvalumab in patients with BCG refractory NMIBC. Since no safety or ...

5. urotoday.com urotoday.com/library-resources/bladder-cancer/146498-the-current-treatment-landscape-of-bcg-unresponsive-non-muscle-invasive-bladder-cancer-immune-checkpoint-inhibitors.html

BCG-unresponsive Non-Muscle Invasive Bladder Cancer We will discuss the currently available evidence and key ongoing studies for immune checkpoint inhibitor therapy in the BCG-unresponsive NMIBC disease space.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)04349-7/fulltext

273MO DURANCE: A phase Ib/II study to assess the safety ... A phase Ib/II study to assess the safety and activity of durvalumab (MEDI4736) in combination with S-488210/S-488211 vaccine in non-muscle invasive bladder ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.778

Feasibility and safety results from RAD-IO A multi-stage trial of durvalumab (Medi4736) with chemoradiotherapy with 5-fluorouracil and mitomycin C in patients with muscle-invasive bladder cancer.

8. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-regimen-reduced-the-risk-of-disease-recurrence-or-death-by-32-percent-in-high-risk-non-muscle-invasive-bladder-cancer-in-the-POTOMAC-Phase-III-trial.html

IMFINZI® (durvalumab) regimen reduced the risk of ... Positive results from the POTOMAC Phase III trial showed adding one year of treatment with AstraZeneca's IMFINZI® (durvalumab) to BCG induction ...