Durvalumab for Bladder Cancer

Not currently recruiting at 31 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-PD-L1, Anti-CTLA-4

Disqualifiers: Pregnancy, Autoimmune disorders, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how durvalumab, a type of immunotherapy, affects bladder cancer when used after surgery, chemotherapy, and radiotherapy. The goal is to determine if it can help prevent the cancer from returning or spreading. Participants will either receive durvalumab or undergo close monitoring without it. The trial seeks individuals who have completed treatment for bladder cancer and show no signs of the disease spreading beyond the bladder. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days of starting the study, except for certain corticosteroids at low doses. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that durvalumab is likely to be safe for humans?

Research shows that durvalumab is generally safe, with most people finding the side effects manageable. Some studies found that a few patients experienced serious side effects, such as blood in urine, lung infections, and skin rashes, though these were rare.

Overall, other studies with bladder cancer patients have shown durvalumab to be safe. This information may provide reassurance for those considering participation in a trial with this treatment. ^{1 2 3 4 5}

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

Researchers are excited about Durvalumab for bladder cancer because it represents a novel approach compared to traditional treatments like chemotherapy and surgery. Unlike these standard options, which mainly aim to remove or kill cancer cells, Durvalumab is an immunotherapy that works by targeting and blocking the PD-L1 protein. This action helps the immune system recognize and attack cancer cells more effectively. This new mechanism of action could offer hope for improved outcomes and fewer side effects for patients with bladder cancer.

What evidence suggests that durvalumab might be an effective treatment for bladder cancer?

Research has shown that durvalumab, one of the treatments in this trial, holds promise for treating bladder cancer. One study found that durvalumab reduced the risk of death by 25% compared to standard treatments. For patients with PD-L1-positive bladder cancer, durvalumab proved particularly effective. Another study found that combining durvalumab with BCG, a bladder cancer vaccine, can slow the disease's progression to more severe stages. These findings suggest that durvalumab could be a good option for managing bladder cancer. Participants in this trial will either receive durvalumab or undergo surveillance. ^{1 3 4 5 6}

Who Is on the Research Team?

Wassim Kassouf

Principal Investigator

The Research Institute of the McGill University, Montreal QC Canada

Are You a Good Fit for This Trial?

Adults over 18 with muscle-invasive bladder cancer, who've completed surgery, chemo, and radiotherapy can join this trial. They should have no metastatic disease, a life expectancy over 6 months, good organ function, and be within certain weight and health status limits. Women/men of childbearing potential must agree to use effective contraception for 3 months post-treatment.

Inclusion Criteria

Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits placed on patients being considered for this trial.

Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.

My bladder cancer was between stages T2 to T4a without spread to lymph nodes or distant organs at diagnosis.

Exclusion Criteria

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

I have been treated with specific immune system targeting drugs before.

I haven't had serious autoimmune or inflammatory disorders in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants undergo surgery, chemotherapy, and radiotherapy for muscle-invasive bladder cancer

12 weeks

Adjuvant Treatment

Participants receive durvalumab to assess its effects on bladder cancer post initial treatment

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab

Trial Overview The study is testing the effects of Durvalumab on bladder cancer when given after trimodality therapy (TMT), which includes surgery, chemotherapy, and radiation therapy. The goal is to see if adding Durvalumab improves outcomes compared to just TMT alone.

How Is the Trial Designed?

Group I: Surveillance Active Control 1 Intervention

Group II: Durvalumab Active Control 1 Intervention

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

AstraZeneca

Industry 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 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 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]

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]

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]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

In a study involving 867 patients with previously treated urinary tract carcinoma, fixed-dose durvalumab administered every four weeks demonstrated an acceptable safety profile, with 51% of patients experiencing adverse events and only 11% having immune-mediated adverse events.

The treatment showed clinical activity with a median overall survival of 7.0 months and an objective response rate of 18%, indicating that durvalumab can be an effective option for patients who have progressed after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results of STRONG: An open-label, multicenter, phase 3b study of fixed-dose durvalumab monotherapy in previously treated patients with urinary tract carcinoma. Sonpavde, GP., Sternberg, CN., Loriot, Y., et al.[2022]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27269937/

Safety and Efficacy of Durvalumab (MEDI4736), an ... - PubMed Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, ...

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

Feasibility and safety results from RAD-IO Recent phase 3 results with peri-operative durvalumab show a 25% reduction in the risk of death compared to standard of care. Methods: RADIO is ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03528694

Study Details | NCT03528694 | Assessment of Efficacy and ... The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic ...

4. imfinzihcp.com imfinzihcp.com/bladder-cancer/muscle-invasive/efficacy.html

Efficacy and Clinical Trial Data for IMFINZI® (durvalumab) Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), ...

5. 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 ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.67.9761

Safety and Efficacy of Durvalumab (MEDI4736), an Anti– ... Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with UBC, many of whom were heavily ...