Durvalumab + Chemotherapy for Bladder Cancer

(NIAGARA Trial)

Recruiting at 171 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

1063 Participants Needed

Trial Summary

What is the purpose of this trial?

A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer

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.

What evidence supports the effectiveness of the drug combination Durvalumab and chemotherapy for bladder cancer?

Research shows that combining gemcitabine and cisplatin, which are part of the chemotherapy regimen, has been effective in treating bladder cancer with less toxicity compared to older treatments. Additionally, drugs like Durvalumab, which target the immune system, have shown promise in treating bladder cancer, especially after other treatments have failed. ^{1 2 3 4 5}

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

Durvalumab, when used with radiation therapy, has been shown to be safe in bladder cancer patients. Cisplatin, a chemotherapy drug often used in combination treatments, can cause side effects like nausea, vomiting, and kidney issues, but these are generally manageable. Durvalumab and other similar drugs are generally well-tolerated, with common side effects including fatigue and decreased appetite. ^{2 5 6 7 8}

How does the drug Durvalumab combined with chemotherapy differ from other treatments for bladder cancer?

Durvalumab is a unique drug because it is a monoclonal antibody that enhances the immune system's response against cancer cells by blocking a specific protein interaction. When combined with chemotherapy, it offers a novel approach compared to traditional chemotherapy alone, potentially improving survival in patients with advanced bladder cancer who have not responded to platinum-based treatments. ^{4 9 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

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

[Immunotherapy for Bladder Cancer]. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Atezolizumab in invasive and metastatic urothelial carcinoma. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Therapy of metastatic bladder carcinoma. [2020]

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

6. 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]

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

Complete remission with immunotherapy: Case report of a patient with metastatic bladder cancer to the humerus. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Approved checkpoint inhibitors in bladder cancer: which drug should be used when? [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

10. United States 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. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison. [2021]

12. United States 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. [2023]