What side effects are associated with this type of intervention?

Common treatments for bladder cancer, particularly those involving immune checkpoint inhibitors like Durvalumab and TGF-beta receptor inhibitors like Vactosertib, can cause a range of side effects. Durvalumab, an anti-PD-L1 antibody, often leads to immune-related adverse events such as fatigue, rash, diarrhea, and more severe autoimmune conditions like colitis, hepatitis, and pneumonitis. TGF-beta receptor inhibitors like Vactosertib may cause fatigue, nausea, diarrhea, and potential cardiovascular issues. Combining these treatments may heighten the risk of immune-related side effects, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of bladder cancer, particularly those targeting the PD-1/PD-L1 pathway. Durvalumab, an anti-PD-L1 antibody, is one such drug that boosts the immune system's activity against cancer cells. Other similar FDA-approved drugs include Atezolizumab and Pembrolizumab, both of which are also anti-PD-L1 antibodies. These drugs have shown efficacy in treating advanced or metastatic urothelial carcinoma, often after the failure of platinum-based chemotherapy. The combination of these immunotherapies with other agents, such as TGF-beta receptor inhibitors like Vactosertib, is currently being studied to enhance the immune response by reducing immunosuppressive signals.

What other types of research exist?

Promising novel alternatives for bladder cancer treatment in 2024 include: 1) Enfortumab Vedotin, an antibody-drug conjugate targeting Nectin-4, which has shown efficacy in patients previously treated with PD-1/PD-L1 inhibitors. 2) Sacituzumab Govitecan, another antibody-drug conjugate targeting Trop-2, which has demonstrated activity in metastatic urothelial carcinoma. 3) Combination therapies such as Nivolumab plus Ipilimumab, which target PD-1 and CTLA-4 pathways respectively, offering a dual checkpoint blockade approach. These alternatives provide new mechanisms and combination strategies to enhance anti-tumor immune responses.

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PD-L1 Inhibitor

Vactosertib + Durvalumab for Bladder Cancer

Phase 2

Waitlist Available

Led By Lawrence Fong, MD

Research Sponsored by MedPacto, Inc.

Eligibility Criteria Checklist

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

Must have

Recurrent disease after any prior platinum-based chemotherapy regimen or ineligible for platinum therapy

Prior anti-PD-(L)1 treatment

Must not have

History of leptomeningeal carcinomatosis

Active or prior documented autoimmune or inflammatory disorders

Timeline

Screening 3 weeks

Treatment Varies

Follow Up overall study period up to 3years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, Durvalumab and Vactosertib, in patients with urothelial cancers who did not respond to previous treatments. Durvalumab helps the immune system attack cancer cells, while Vactosertib blocks signals that help cancer cells grow.

Who is the study for?

This trial is for adults with advanced urothelial bladder cancer that didn't respond to previous anti-PD-1/PD-L1 treatments. Participants must be relatively healthy (ECOG 0 or 1), have a life expectancy of at least 12 weeks, and weigh over 30 kg. They should not have other cancers, serious illnesses like heart failure, active infections including hepatitis B/C or HIV, unresolved toxic effects from past cancer therapy (except hair loss or skin changes), or a history of organ transplant.

What is being tested?

The study is testing the combination of vactosertib with durvalumab in patients whose urothelial carcinoma has not improved after treatment with PD-1/PD-L1 inhibitors. It's an open-label Phase 2 trial aiming to see if this combo can increase the overall response rate—meaning it helps reduce the size of tumors.

What are the potential side effects?

Possible side effects include immune-related reactions such as inflammation in various organs, fatigue, digestive issues like nausea and diarrhea, skin problems like rash and itching, potential liver function changes, and increased risk for infections due to immune system suppression.

Eligibility Criteria

Inclusion Criteria

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

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My cancer came back after platinum-based treatment or I can't have platinum therapy.

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I have previously received anti-PD-(L)1 therapy.

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

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My cancer originates from the urinary system and cannot be removed by surgery.

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My cancer can be measured by scans.

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My body weight is over 30 kg.

Exclusion Criteria

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

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I have had cancer spread to the lining of my brain and spinal cord.

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I have or had an autoimmune or inflammatory disorder.

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I have had another type of cancer in the past.

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I do not have an active infection like TB, hepatitis B or C, or HIV.

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I do not have any uncontrolled illnesses like infections or heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ overall study period up to 3years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~overall study period up to 3years

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

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate

Secondary study objectives

Best Response

Duration of Response

Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]

+4 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Vactosertib+DurvalumabExperimental Treatment1 Intervention

Vactosertib will be administered in combination with standard dose of durvalumab every four weeks.

0 / 11Eligibility 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, particularly advanced or metastatic cases, often involve immune checkpoint inhibitors like Durvalumab, which is an anti-PD-L1 antibody. These inhibitors work by blocking the PD-L1 pathway, a mechanism that cancer cells use to evade the immune system. By inhibiting this pathway, Durvalumab boosts the immune system's ability to recognize and attack cancer cells. Vactosertib, a TGF-beta receptor inhibitor, complements this by reducing immunosuppressive signals in the tumor microenvironment, further enhancing the immune response. This dual approach is significant for bladder cancer patients as it aims to overcome the cancer's defenses and improve the effectiveness of the immune system in targeting and destroying cancer cells.