Radiation Therapy and Durvalumab With or Without Tremelimumab in Treating Participants With Unresectable, Locally Advanced, or Metastatic Bladder Cancer

Bladder Urothelial Carcinoma Clinical Trial

Official title: Phase II Study of Radiation Therapy and Anti-PD-L1 Checkpoint Inhibitor (Durvalumab) With or Without Anti-CTLA-4 Inhibition (Tremelimumab) in Patients With Unresectable, Locally Advanced, or Metastatic Urothelial Bladder Cancer That Are Ineligible or Refusing Chemotherapy

Status Active, not recruiting

Clinical Trial Summary

This phase II trial studies the side effects and how well radiation therapy and durvalumab with or without tremelimumab work in treating participants with bladder cancer that cannot be removed by surgery, has spread to nearby tissue or lymph nodes, or that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving radiation therapy and durvalumab with or without tremelimumab will work better in treating participants with bladder cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the safety profile of radiation therapy (RT) and durvalumab with or without tremelimumab. (Safety lead-in cohort) II. To determine the median progression-free survival with RT and durvalumab with or without tremelimumab. (Expansion cohort)

SECONDARY OBJECTIVES:

I. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of local control of irradiated bladder tumor.

II. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of pathologic complete response (CR) rate of irradiated bladder tumor.

III. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms overall response rate.

IV. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of abscopal response rate.

V. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of duration of response.

VI. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of disease specific survival.

VII. To assess the efficacy of RT and durvalumab with or without tremelimumab in terms of overall survival.

VIII. To further determine the safety and tolerability of RT + durvalumab with or without tremelimumab (expansion cohorts).

EXPLORATORY OBJECTIVES:

I. To explore the immunologic changes associated with the combination of durvalumab and RT +/- tremelimumab.

OUTLINE: Participants are randomized to 1 of 2 regimens.

REGIMEN A: Participants receive durvalumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Participants also undergo external beam radiation therapy (EBRT) for 5 fractions beginning on day 8 of course 1.

REGIMEN B:

Participants receive tremelimumab IV over 60 minutes on day 1 for up to 2 courses and durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression of unacceptable toxicity. Participants also receive undergo EBRT for 5 fractions beginning on day 8 of course 1.

After completion of study treatment, participants are followed up at 8 weeks and then every 12 and 16 weeks. ;

Related Conditions & MeSH terms

• Bladder Urothelial Carcinoma
• Stage IV Bladder Cancer AJCC v8
• Stage IVA Bladder Cancer AJCC v8
• Stage IVB Bladder Cancer AJCC v8
• Urinary Bladder Neoplasms

• NCT number: NCT03601455
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 26, 2018
• Completion date: January 31, 2026