Durvalumab + Chemotherapy for Bladder Cancer

(NIAGARA Trial)

Not currently recruiting at 225 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Metastatic disease, Prior radiotherapy, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment plan for people with muscle-invasive bladder cancer. Researchers aim to determine if adding the drug durvalumab (an immunotherapy) to standard chemotherapy (gemcitabine and cisplatin) before surgery can provide benefits, and how well durvalumab works on its own afterward. Participants are divided into two groups: one receiving both chemotherapy and durvalumab, and the other receiving only chemotherapy. Suitable candidates are those planning to undergo bladder removal surgery and who have not yet received treatments like chemotherapy or immunotherapy for their cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using immunosuppressive medications (drugs that lower the body's immune response) within 14 days before starting the study treatment, with some exceptions like certain steroids. If you are on other medications, the protocol does not specify, so it's best to discuss with the trial team.

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

Research has shown that combining durvalumab with the chemotherapy drugs gemcitabine and cisplatin yields promising results for treating certain cancers. In a study on upper tract urothelial carcinoma, some patients experienced complete responses, meaning the treatment completely removed signs of cancer, indicating its effectiveness.

Regarding safety, the treatment has generally been well-tolerated. Reports indicate that 67.8% of patients did not experience significant issues or cancer progression for 24 months after starting treatment.

While side effects can occur, research suggests that the combination of durvalumab and chemotherapy is reasonably safe. Although risks exist, current evidence considers the treatment safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

Researchers are excited about combining Durvalumab with chemotherapy for bladder cancer because it introduces a new approach by integrating an immunotherapy component. Unlike standard treatments that mainly rely on chemotherapy, Durvalumab, an immune checkpoint inhibitor, works by enhancing the body's immune response to target and destroy cancer cells. This combined approach has the potential to not only improve the effectiveness of treatment but also to offer a more durable response, as it leverages the body's own defenses to fight the cancer. By adding Durvalumab to the traditional chemotherapy regimen of Cisplatin and Gemcitabine, there is hope for better management of the disease and improved patient outcomes.

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

This trial will compare the effectiveness of combining durvalumab with chemotherapy drugs, specifically cisplatin and gemcitabine, against chemotherapy alone for treating bladder cancer. Studies have shown that the combination of durvalumab with chemotherapy looks promising. One study found that this combination helped patients live longer compared to chemotherapy alone. Another study showed that some patients had complete responses, with no signs of cancer after treatment. The FDA recognized durvalumab as effective against urothelial carcinoma, a type of bladder cancer, and approved it in 2017. This evidence suggests that using durvalumab with chemotherapy could effectively treat muscle-invasive bladder cancer. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with muscle-invasive bladder cancer (MIBC) who haven't had chemo or immunotherapy for it, are expected to live at least 12 weeks, and plan to have their bladder removed. They should be fairly active (ECOG 0-1), not have advanced cancer spread, no recent vaccines or immune therapies, and can't be on strong immune-suppressing drugs.

Inclusion Criteria

I am fully active or can carry out light work.

My bladder cancer is operable and has not spread beyond nearby tissues or lymph nodes.

I am scheduled for a surgery to remove my bladder.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

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

I haven't taken strong immune system suppressing drugs in the last 14 days, except for minor exceptions like inhalers or low-dose steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive Durvalumab in combination with Gemcitabine and Cisplatin

6-12 weeks

Adjuvant Treatment

Participants receive Durvalumab alone

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Gemcitabine

Trial Overview The study tests Durvalumab combined with Gemcitabine+Cisplatin before bladder removal surgery and then Durvalumab alone after surgery. It aims to see if this combo is effective and safe in treating MIBC compared to current treatments.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 3 Interventions

Chemotherapy + Durvalumab

Group II: Arm 2 Active Control 2 Interventions

Chemotherapy alone

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

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

The combination of durvalumab and cabozantinib was found to be safe in a phase 2 study with 16 patients, showing no severe treatment-related adverse events in the first two cycles, although common mild side effects included fatigue and diarrhea.

Preliminary results indicated that 37.5% of patients experienced objective responses, including two complete responses, suggesting that this combination therapy may be effective for patients with advanced metastatic urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial. Marandino, L., Raggi, D., Calareso, G., et al.[2021]

Atezolizumab, an anti-PD-L1 monoclonal antibody, has shown durable responses in treating locally advanced and metastatic urothelial cancer, especially in patients who have failed platinum-based chemotherapy or are ineligible for cisplatin.

The treatment with atezolizumab has a more favorable toxicity profile compared to traditional cytotoxic chemotherapy, making it a promising option for patients with advanced bladder cancer, although further research is needed to identify additional predictive markers for response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. Crist, M., Balar, A.[2019]

Five checkpoint inhibitors, including pembrolizumab and atezolizumab, are FDA-approved for treating advanced metastatic urothelial carcinoma after progression on cisplatin-based chemotherapy, showing significant clinical efficacy.

For patients who are eligible for cisplatin, standard first-line treatment remains platinum-based chemotherapy, but for those who progress, pembrolizumab has shown superior results compared to standard chemotherapy in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approved checkpoint inhibitors in bladder cancer: which drug should be used when? Ghatalia, P., Zibelman, M., Geynisman, DM., et al.[2020]

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]

In a phase II study involving 61 patients with muscle-invasive urothelial carcinoma, the addition of neoadjuvant durvalumab to standard chemotherapy resulted in a high event-free survival (EFS) rate of 76% at 2 years, indicating promising efficacy in this treatment approach.

The study also reported an overall survival (OS) rate of 85% at 2 years, although 42% of patients experienced grade 3 or 4 treatment-related adverse events during the neoadjuvant phase, highlighting the need to balance efficacy with safety in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17. Cathomas, R., Rothschild, SI., Hayoz, S., et al.[2023]

The gemcitabine and cisplatin (CG) combination has emerged as the new standard of care for metastatic bladder carcinoma, showing similar effectiveness to the previous standard M-VAC regimen but with less toxicity.

Novel treatments like pemetrexed and vinflunine are showing promise in clinical trials, with pemetrexed demonstrating a 28% response rate and vinflunine providing an 18% response rate in pretreated patients, indicating potential for improved outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. Iaffaioli, RV., Milano, A., Caponigro, F.[2020]

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

Citations

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Safety and efficacy of neoadjuvant immunotherapy with ... Combination of durvalumab with platin-based chemotherapy, especially cisplatin, showed promising activity in UTUC, with the occurrence of complete responses.

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

Neoadjuvant Immunotherapy in Bladder Cancer Perioperative chemoimmunotherapy with durvalumab plus cisplatin/gemcitabine showed greater OS than chemotherapy alone in the NIAGARA trial. The NEMIO trial ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02516241

NCT02516241 | Study of MEDI4736 (Durvalumab) With or ... This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of MEDI4736 (Durvalumab) monotherapy

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ASCO GU 2025: iNDUCT: Safety and Efficacy of ... 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6452813/

Durvalumab for the management of urothelial carcinoma Durvalumab is a safe and effective therapeutic option in UC and was granted FDA approval in May 2017 based on the results of the Phase I/II trial.

6. clinicaltrial.be clinicaltrial.be/en/details/6356?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Durvalumab+ Gemcitabine/Cisplatin (Neoadjuvant ... Secondary outcomes 6 · Event-free Survival at 24 Months (EFS24) Per Central Review Defined as Time From Randomization to Event · Proportion of ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03732677

Study Details | NCT03732677 | Durvalumab+ Gemcitabine/ ... A global study to determine the efficacy and safety of Durvalumab in combination with Gemcitabine+Cisplatin for neoadjuvant treatment and Durvalumab alone for ...