What side effects are associated with this type of intervention?

Common treatments for bladder cancer, particularly those involving PD-L1 inhibitors like Durvalumab, often include chemotherapy and immunotherapy. The known side effects of these treatments can vary. Chemotherapy side effects typically include nausea, vomiting, hair loss, fatigue, and increased risk of infections due to lowered white blood cell counts. Immunotherapy with PD-L1 inhibitors, such as Durvalumab, can cause immune-related adverse events including colitis, hepatitis, pneumonitis, endocrinopathies, and skin reactions. These immune-related side effects occur because the treatment can cause inflammation in various organ systems.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of bladder cancer, particularly for patients who have progressed after platinum-based chemotherapy. Atezolizumab, an anti-PD-L1 therapy, was approved based on the IMvigor210 study. Pembrolizumab, an anti-PD-1 therapy, has also been approved for advanced urothelial carcinoma, as demonstrated in the KEYNOTE-045 trial. These therapies, similar to Durvalumab, target the PD-1/PD-L1 pathway to enhance the immune system's ability to fight cancer.

What other types of research exist?

Promising alternatives to Durvalumab for bladder cancer patients include Pembrolizumab and Nivolumab, both of which are PD-1 inhibitors. Pembrolizumab has been shown to be effective as a second-line therapy for advanced urothelial carcinoma, and Nivolumab has demonstrated efficacy in recurrent metastatic urothelial carcinoma. Additionally, Enfortumab Vedotin, an antibody-drug conjugate, and Erdafitinib, a pan-FGFR inhibitor, are novel options that have shown promising results in clinical trials for advanced or metastatic urothelial carcinoma.

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Alkylating agents

Chemotherapy + Durvalumab for Bladder Cancer

Phase 2

Recruiting

Led By Matthew Campbell

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must be ≥18 years of age.

Patients must have histological diagnosis of urothelial carcinoma of the bladder and must meet criteria for stage cTanyN1-3M0 disease via AJCC 8th edition staging criteria

Must not have

History of allogeneic organ transplant.

Has a known additional malignancy that is progressing or requires active treatment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if adding durvalumab to standard chemotherapy improves outcomes for bladder cancer patients whose cancer has spread to pelvic lymph nodes. Durvalumab helps the immune system attack cancer cells, potentially making the treatment more effective.

Who is the study for?

This trial is for adults with bladder cancer that has spread to pelvic lymph nodes but not beyond. They must be in good physical condition, have a life expectancy of at least 12 weeks, weigh over 30 kg, and have proper heart and organ function. Women who can bear children need a negative pregnancy test and agree to use contraception.

What is being tested?

The study compares standard chemotherapy (cisplatin) with or without Durvalumab in patients with urothelial carcinoma of the bladder. Participants will be randomly assigned to receive either just chemotherapy or chemotherapy plus Durvalumab, which continues as maintenance for up to one year.

What are the potential side effects?

Possible side effects include immune-related reactions due to Durvalumab affecting organs like the liver or lungs, infusion reactions from drug administration, fatigue, nausea from chemotherapy drugs like Cisplatin and Doxorubicin Hydrochloride, blood disorders such as low counts of white cells or platelets.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My bladder cancer is at a specific stage where it has spread to nearby lymph nodes but not to distant parts of my body.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I weigh more than 30 kilograms.

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Your blood, kidney, liver, and blood clotting functions are within normal levels.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had an organ transplant from another person.

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I have another cancer that is getting worse or needs treatment.

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I have severe heart failure.

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I experience significant numbness or pain due to nerve damage.

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I have moderate to severe hearing loss.

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I have been treated with immunotherapy for another cancer.

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I have previously been treated with drugs targeting PD-1 or PD-L1.

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I do not have any serious ongoing illnesses that could affect my participation in the study.

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I do not have an active tuberculosis infection.

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I do not have active Hepatitis B, Hepatitis C, or HIV.

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I have had an autoimmune disease in the last 2 years.

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I do not have an active infection needing IV antibiotics or a severe illness requiring hospitalization.

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My cancer has spread to lymph nodes outside my pelvis or to organs.

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I am allergic to methotrexate, vinblastine, doxorubicin, cisplatin, durvalumab, or similar drugs.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: Intervention with dose-dense MVAC plus DurvalumabExperimental Treatment6 Interventions

Durvalumab will be administered one week prior to the initial cycle of dose-dense MVAC and then with each additional cycle of dose-dense MVAC on Arm B

Group II: Arm A: Standard of Care with dose-dense MVACExperimental Treatment6 Interventions

The patient will receive treatment every 14 days for up to 6 cycles in the neoadjuvant setting.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Methotrexate

2019

Completed Phase 4

~4400

Durvalumab

2017

Completed Phase 2

~3750

Cisplatin

2013

Completed Phase 3

~3120

Vinblastine

1998

Completed Phase 3

~5410

Doxorubicin Hydrochloride

2019

Completed Phase 3

~17860

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for bladder cancer include chemotherapy and immunotherapy. Chemotherapy, such as cisplatin-based regimens, works by damaging the DNA of rapidly dividing cancer cells, leading to cell death. Immunotherapy, particularly PD-L1 inhibitors like Durvalumab, enhances the body's immune response against cancer cells. Durvalumab blocks the PD-L1 protein on cancer cells, preventing them from evading immune detection and destruction. This is crucial for bladder cancer patients as it offers a targeted approach to boost the immune system's ability to fight cancer, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

[The role of immunotherapy in the modern treatment of urothelial carcinoma].