Durvalumab + Chemotherapy for Bladder Cancer

Recruiting at 46 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Contraindicated chemotherapy

Disqualifiers: Metastatic disease, Inoperable tumors, others

Stay on Your Current Meds You can continue your current medications while participating

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use immunosuppressive medication within 14 days before starting durvalumab, and you should not take any medication that is contraindicated (not recommended) with the chemotherapy used in the trial.

What data supports the effectiveness of the drug combination Durvalumab + Chemotherapy for Bladder Cancer?

Durvalumab has shown meaningful clinical activity and durable response in patients with advanced bladder cancer, as seen in several studies. It is well-tolerated and has been part of recent advances in bladder cancer treatment, suggesting its potential effectiveness when combined with chemotherapy. ^{1 2 3 4 5}

Is the combination of Durvalumab and chemotherapy safe for treating bladder cancer?

Durvalumab is generally well-tolerated in bladder cancer treatment, with common side effects including fatigue, decreased appetite, and nausea. Studies have shown that combining Durvalumab with other treatments like radiation is safe, and it has been used in various cancer treatments with manageable side effects. ^{2 6 7 8 9}

How is the drug Durvalumab unique for treating bladder cancer?

Durvalumab is unique because it is an immune checkpoint inhibitor that targets PD-L1, helping the immune system attack cancer cells, and it has shown promising results in patients who are not eligible for standard chemotherapy. It is often combined with other treatments like chemotherapy or radiation to enhance its effectiveness in advanced bladder cancer. ^{1 2 3 9 10}

What is the purpose of this trial?

The Phase IIIb NIAGARA-2 study aims to expand on the data from the Phase III NIAGARA study by investigating perioperative durvalumab in combination with investigator-selected cisplatin-based neoadjuvant chemotherapy (either ddMVAC or gemcitabine/cisplatin) in a clinical practice setting.

Eligibility Criteria

This trial is for individuals with muscle-invasive bladder cancer who can undergo chemotherapy. Specific eligibility details are not provided, but typically participants must be adults in good general health and have no conflicting medical conditions or treatments.

Inclusion Criteria

Minimum life expectancy of 12 weeks at first dose of study medication

I haven't had chemotherapy or immunotherapy for my bladder cancer.

My cancer is at a specific stage and may involve certain cells.

Exclusion Criteria

I am not on any medication that conflicts with my chemotherapy treatment.

My tumor cannot be removed surgically and is attached to the pelvic wall.

My cancer has spread to lymph nodes or other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant durvalumab combined with ddMVAC or gemcitabine/cisplatin prior to radical cystectomy

Up to 6 months

Radical Cystectomy

Participants undergo radical cystectomy following neoadjuvant chemotherapy

Surgical procedure

Follow-up

Participants are monitored for safety, tolerability, and efficacy outcomes including event-free survival, disease-free survival, and overall survival

Up to 3 years

Treatment Details

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine

Trial Overview The NIAGARA-2 study tests perioperative durvalumab (an immune checkpoint inhibitor) combined with a choice of two cisplatin-based chemotherapies: ddMVAC or gemcitabine/cisplatin, to see how well they work together before and after surgery.

Participant Groups

Group I: gem/cis cohort Experimental Treatment 3 Interventions

Durvalumab + chemotherapy

Group II: ddMVAC cohort Experimental Treatment 5 Interventions

Durvalumab + chemotherapy

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

Findings from Research

In a study of patients with metastatic urothelial carcinoma, treatment with durvalumab led to significant improvements in health-related quality of life (HRQOL) and disease-related symptoms, as measured by the FACT-Bl and EORTC QLQ-C30 questionnaires.

The improvements in patient-reported outcomes were correlated with better tumor shrinkage and reductions in inflammatory biomarkers, suggesting that durvalumab not only helps manage cancer symptoms but may also positively influence systemic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108. O'Donnell, PH., Arkenau, HT., Sridhar, SS., et al.[2021]

Durvalumab, an immune-checkpoint inhibitor, has shown to be well-tolerated and effective in producing significant and lasting responses in patients with advanced urothelial bladder cancer, addressing a critical need for better treatment options.

The potential for combining durvalumab with other therapies may enhance treatment strategies for urothelial carcinoma, but further research is necessary to identify biomarkers that can predict which patients will benefit most from these immune-oncology treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in urothelial cancers. Lavaud, P., Hamilou, Z., Loriot, Y., et al.[2018]

Durvalumab, a monoclonal antibody targeting PD-L1, showed a manageable safety profile in patients with advanced urothelial bladder cancer, with common side effects including fatigue and diarrhea, but no severe (grade 4 or 5) adverse events reported.

The treatment demonstrated a 31% overall response rate, with a significantly higher response of 46.4% in patients with PD-L1-positive tumors, indicating that PD-L1 expression may play a crucial role in the efficacy of durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. Massard, C., Gordon, MS., Sharma, S., et al.[2022]

Recent advancements in the treatment of advanced-stage urothelial carcinoma, a common type of bladder cancer, include the FDA approval of several immune checkpoint inhibitors such as nivolumab, pembrolizumab, and atezolizumab.

Despite these promising new therapies, clinicians face challenges in selecting the most effective treatment options for patients, particularly in determining the best first-line or second-line therapies to improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. Flaig, TW.[2019]

The SUBDUE-1 trial is a phase I study evaluating the safety and immunological efficacy of sub-urothelial injections of durvalumab in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer, involving three dose levels (25, 75, 150 mg) to determine the optimal dose for future trials.

If successful, this local administration method may reduce tumor recurrence and progression while minimizing immunological side effects and costs compared to traditional systemic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (SUBDUE-1, SUB-urothelial DUrvalumab injection-1 study): clinical trial protocol. Moe, A., Liow, E., Redfern, A., et al.[2021]

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

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]

References

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

Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Durvalumab in urothelial cancers. [2018]

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

Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer. [2022]

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

An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer. [2022]

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

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma. [2019]

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

A phase I open label dose-escalation study to evaluate the tolerability, safety and immunological efficacy of sub-urothelial durvalumab injection in adults with muscle-invasive or high-risk non-muscle-invasive bladder cancer (SUBDUE-1, SUB-urothelial DUrvalumab injection-1 study): clinical trial protocol. [2021]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

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

Concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: results from phase II study, BTCRC-GU15-023. [2023]

10. 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]