Propranolol Hydrochloride and Pembrolizumab for the Treatment of Recurrent or Metastatic Urothelial Cancer
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|ClinicalTrials.gov Identifier: NCT04848519|
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : June 9, 2022
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: Pembrolizumab Drug: Propranolol Hydrochloride||Phase 2|
I. To evaluate the anti-tumor activity of the combination of propranolol hydrochloride and pembrolizumab by assessing the overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.).
I. To evaluate the efficacy of the combination as measured by progression free survival (PFS; from treatment initiation until disease progression, death due to disease, or lost to follow up) and overall survival (OS; from treatment initiation until death due to any cause or loss to follow up), and safety as measured by incidence of adverse events assessed up to 2 years.
I. To assess tissue-based assays in archival tissue and correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells (MDSC), blood inflammatory markers and cytokines.
Patients receive propranolol hydrochloride orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for propranolol hydrochloride and every 3 or 6 weeks for pembrolizumab for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 12 weeks for up to 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Propranolol Hydrochloride and Pembrolizumab in Patients With Recurrent or Metastatic Urothelial Carcinoma: A Single Center Phase II Trial|
|Actual Study Start Date :||May 20, 2021|
|Estimated Primary Completion Date :||January 1, 2024|
|Estimated Study Completion Date :||January 1, 2024|
Experimental: Treatment (propranolol hydrochloride, pembrolizumab)
Patients receive propranolol hydrochloride PO BID on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for propranolol hydrochloride and every 3 or 6 weeks for pembrolizumab for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Propranolol Hydrochloride
Other Name: Inderal
- Overall response rate (ORR) [ Time Frame: Up to 2 years post treatment ]Defined as the proportion of subjects with a best overall response of complete or partial response as assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. This will be summarized with the 2-sided 95% confidence interval using the Clopper-Pearson method.
- Progression free survival (PFS) [ Time Frame: From start of study treatment to the first objective documentation of radiological disease progression or death due to any cause, assessed up to 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) [ Time Frame: From the start of study treatment to the date of death due to any cause, assessed up to 2 years ]Kaplan-Meier methods will be used to estimate median survival time or time-specific survival rate with 95% confidence interval for OS.
- Incidence of adverse events [ Time Frame: Up to 28 days ]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.
- Immune profile and changes in selected biomarkers and cell subsets [ Time Frame: Baseline up to 2 years ]Correlative changes in peripheral T-cell subsets, myeloid derived suppressor cells, blood inflammatory markers and blood cytokines before and after treatment, will first be described by summary statistics. Descriptive statistics on continuous data will include mean, median, standard deviation, and range (as well as geometric means and geometric coefficient of variation for pharmacokinetic parameters), while categorical data will be summarized using frequency counts and percentages. Graphical summaries of the data may be presented. Their correlation with clinical efficacy endpoints will be carried out by logistic regression model for ORR or Cox proportional hazard mode for time to even outcomes (OS or PFS).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04848519
|Contact: Bassel Nazha, MD, MPHemail@example.com|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Wilena Session 404-778-3448 firstname.lastname@example.org|
|Principal Investigator: Bassel Nazha, MD, MPH|
|Principal Investigator:||Bassel Nazha, MD, MPH||Emory University Hospital/Winship Cancer Institute|