Immune Checkpoint Inhibitors With or Without Propranolol Hydrochloride In Patients With Urothelial Carcinoma
- Conditions
- Locally Advanced Bladder Urothelial CarcinomaLocally Advanced Renal Pelvis Urothelial CarcinomaLocally Advanced Ureter Urothelial CarcinomaLocally Advanced Urethral Urothelial CarcinomaLocally Advanced Urothelial CarcinomaMetastatic Bladder Urothelial CarcinomaMetastatic Renal Pelvis Urothelial CarcinomaMetastatic Ureter Urothelial CarcinomaMetastatic Urethral Urothelial CarcinomaMetastatic Urothelial Carcinoma
- Interventions
- Registration Number
- NCT04848519
- Lead Sponsor
- Emory University
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 24
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment (propranolol hydrochloride, immune checkpoint inhibitor) Propranolol Hydrochloride The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (propranolol hydrochloride, immune checkpoint inhibitor) Pembrolizumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (propranolol hydrochloride, immune checkpoint inhibitor) Nivolumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (immune checkpoint inhibitor) Nivolumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (propranolol hydrochloride, immune checkpoint inhibitor) Avelumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (immune checkpoint inhibitor) Pembrolizumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval. Treatment (immune checkpoint inhibitor) Avelumab The specific ICI that the subject would receive will be dependent on the clinical need and associated FDA approval.
- Primary Outcome Measures
Name Time Method Incidence of adverse events 2 years Assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be used to summarize the toxicity profile of the intervention. Toxicities will be tabulated by grade, association, and cycle number.
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) 2 years Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with 95% confidence interval for PFS.
Overall survival (OS) 2 years Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with 95% confidence interval for OS.
Objective Response Rate (ORR) 2 years Defined as the proportion of subjects only receiving avelumab and pembrolizumab as ICI.
Trial Locations
- Locations (1)
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States