Durvalumab + Chemotherapy for Bladder Cancer

Recruiting at 57 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug durvalumab works with chemotherapy in treating bladder cancer. The goal is to determine if this combination benefits those planning to have their bladders surgically removed due to invasive cancer. The study includes two groups, each receiving a different type of chemotherapy with durvalumab. This trial may suit individuals with bladder cancer that hasn't spread, who haven't undergone chemotherapy, and who are scheduled for surgery. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that combining durvalumab with chemotherapy drugs like cisplatin and gemcitabine is generally well-tolerated by patients. While some experienced side effects, most were manageable. Common side effects included tiredness, nausea, and lower white blood cell counts, typical for chemotherapy. Serious side effects were less common but did occur in some cases.

These results suggest the treatment is reasonably safe, especially since durvalumab is already approved for other uses. The trial aims to gather more detailed safety information. Prospective participants should discuss any concerns with their doctor to determine if this treatment is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab for bladder cancer because it represents a fresh approach to treatment. Most existing therapies rely on traditional chemotherapy, but Durvalumab is an immunotherapy that works by targeting and blocking a specific protein called PD-L1. This action helps the immune system recognize and attack cancer cells more effectively. By combining Durvalumab with chemotherapy, there's potential to enhance the overall effectiveness of treatment, offering new hope to patients by potentially improving outcomes compared to standard chemotherapy alone.

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

Research shows that combining durvalumab with chemotherapy may effectively treat bladder cancer. In this trial, participants will be assigned to different treatment arms, each receiving durvalumab with chemotherapy. Earlier studies found that patients who received durvalumab with cisplatin and gemcitabine had a 67.8% chance of their cancer not worsening or returning after 24 months. Specifically, many patients did not experience cancer progression. Additionally, 82.2% of these patients were still alive after this period, indicating a strong potential for longer life. This combination works by using durvalumab to help the immune system fight cancer cells, offering hope for better results in bladder cancer treatment. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00179

The iNDUCT-GETUG V08 Trial | Journal of Clinical Oncology This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39951246/

The iNDUCT-GETUG V08 Trial This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients.

3. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-upper-tract-urothelial-carcinoma/158277-induct-safety-and-efficacy-of-neoadjuvant-immunotherapy-with-durvalumab-in-combination-with-neoadjuvant-chemotherapy-gemcitabine-cisplatin-or-carboplatin-in-patients-with-operable-high-risk-upper-tract-urothelial-carcinoma.html

ASCO GU 2025: iNDUCT - UroToday There is rationale for interest in immunotherapy, given the recent data from NIAGARA in bladder cancer showing an estimated event free survival of 67.8% in the ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666168325002782

Neoadjuvant Immunotherapy in Bladder Cancer At 24 mo, an EFS rate of 67.8% and an OS rate of 82.2% were reported in patients treated with neoadjuvant durvalumab associated with cisplatin and gemcitabine ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer

FDA approves durvalumab for muscle invasive bladder ... The major efficacy outcome was event-free survival (EFS) by blinded independent central review. Overall survival (OS) was an additional efficacy ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO-25-00179

Safety and Efficacy of Neoadjuvant Durvalumab Plus ... This study evaluated safety and efficacy of neoadjuvant chemotherapy (cisplatin or carboplatin + gemcitabine) in combination with durvalumab in these patients.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ueg2.12656

Efficacy, safety and differential outcomes of immune‐ ... The best overall response rate was 28.5% and disease control rate was 65.5%. While extrahepatic and intrahepatic BTC showed similar outcomes, ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT323903

A phase III, randomized, open-label, multicenter, global ... A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for ...