NCT04848519

Immune Checkpoint Inhibitors With or Without Propranolol Hydrochloride In Patients With Urothelial Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This research study is an open label study designed to evaluate the safety and translational correlative changes of the combination of propranolol hydrochloride and immune checkpoint inhibitors (ICI) in subjects with urothelial carcinoma.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety of the combination of propranolol hydrochloride and immune checkpoint inhibitors in urothelial cancer as measured by the incidence of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 SECONDARY OBJECTIVE: I. To describe response and survival outcomes for ICI plus or minus propranolol in patients with urothelial cancer as measured by ORR per RECIST 1.1 (only for subjects receiving avelumab and pembrolizumab as ICI), profession free survival (PFS) and overall survival (OS). TERTIARY/EXPLORATORY OBJECTIVE: I. To measure overall response rate (ORR) along with correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and blood cytokines before and after treatment for patients receiving ICI plus propranolol vs. ICI alone. Available archival tissue will also be collected for tissue-based assays. OUTLINE: Patients who meet eligibility criteria and consent for enrollment in the trial will be on one of the two study cohorts. Assignment to cohorts will be sequentially, in a 1:1 fashion, starting with the ICI plus propranolol cohort. The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. ICI PLUS PROPRANOLOL COHORT: 1\. Propranolol: Participants will remain on propranolol 30mg twice daily for the duration of the trial unless unacceptable toxicity or withdrawal of consent. Patients who develop toxicity and stop propranolol will remain on trial for endpoint measurement. PLUS Pembrolizumab: Participants will receive 200mg IV on Day 1, every 3 weeks. Pembrolizumab would be continued for up to 2 years in the absence of disease progression or unacceptable toxicity. OR Avelumab: Participants will receive Avelumab at a dose of 10 mg per kilogram of body weight, IV on Day 1 every 2 weeks until disease progression or unacceptable toxicity. OR Nivolumab: Participants will receive Nivolumab (480mg) IV on every 4 weeks for up to 1 year or until disease recurrence or discontinuation from the trial. ICI ALONE COHORT: Pembrolizumab: Participants will receive 200mg IV on Day 1, every 3 weeks. Pembrolizumab would be continued for up to 2 years in the absence of disease progression or unacceptable toxicity. OR Avelumab: Participants will receive Avelumab at a dose of 10 mg per kilogram of body weight, IV on Day 1 every 2 weeks until disease progression or unacceptable toxicity OR Nivolumab: Participants will receive Nivolumab (480mg) IV on every 4 weeks for up to 1 year or until disease recurrence or discontinuation from the trial. After completion of study treatment, patients are followed up at 30 days, then every 12 weeks for up to 2 years.

Conditions

• Locally Advanced Bladder Urothelial Carcinoma
• Locally Advanced Renal Pelvis Urothelial Carcinoma
• Locally Advanced Ureter Urothelial Carcinoma
• Locally Advanced Urethral Urothelial Carcinoma
• Locally Advanced Urothelial Carcinoma
• Metastatic Bladder Urothelial Carcinoma
• Metastatic Renal Pelvis Urothelial Carcinoma
• Metastatic Ureter Urothelial Carcinoma
• Metastatic Urethral Urothelial Carcinoma
• Metastatic Urothelial Carcinoma
• Stage IV Bladder Cancer AJCC v8
• Stage IV Renal Pelvis Cancer AJCC v8
• Stage IV Ureter Cancer AJCC v8
• Stage IV Urethral Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Given IV as first line for locally advanced or metastatic urothelial carcinoma who are not eligible for platinum-based chemotherapy; or second line for locally advanced or metastatic urothelial carcinoma after progression on platinum-based chemotherapy
DRUG	Propranolol Hydrochloride	Given PO for patients on the ICI plus propranolol arm
DRUG	Nivolumab	Given IV as adjuvant treatment of urothelial carcinoma in high risk of disease recurrence after undergoing radical resection
DRUG	Avelumab	Given IV as maintenance treatment in locally advanced or metastatic urothelial carcinoma following no progression on first-line platinum-containing chemotherapy

Timeline

• Start date: 2021-05-20
• Primary completion: 2025-10-15
• Completion: 2026-12-04
• First posted: 2021-04-19
• Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study