NCT03601455

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

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
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

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

Interventions

Type	Name	Description
BIOLOGICAL	Durvalumab	Given IV
RADIATION	External Beam Radiation Therapy	Undergo EBRT
BIOLOGICAL	Tremelimumab	Given IV

Timeline

• Start date: 2018-10-26
• Primary completion: 2026-01-31
• Completion: 2027-01-31
• First posted: 2018-07-26
• Last updated: 2025-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study