Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery
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|ClinicalTrials.gov Identifier: NCT03384836|
Recruitment Status : Recruiting
First Posted : December 27, 2017
Last Update Posted : May 9, 2019
|Condition or disease||Intervention/treatment||Phase|
|Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7||Other: Laboratory Biomarker Analysis Biological: Pembrolizumab Drug: Propranolol Hydrochloride||Phase 1 Phase 2|
I. To determine dose limiting toxicities (DLT) of propranolol hydrochloride (propranolol) in combination with fixed dose pembrolizumab in the treatment of melanoma.
II. To evaluate the efficacy of pembrolizumab in combination with propranolol in patients with melanoma, as determined by overall response rate (ORR) per immune-modified Response Evaluation Criteria in Solid Tumors (RECIST) (1).
I. To evaluate the efficacy of pembrolizumab in combination with propranolol in patients with melanoma, as determined by secondary measures of efficacy, including: progression free survival (PFS) and overall survival (OS).
I. To correlate baseline or changes in the levels of biomarkers, like, peripheral T-cell subsets/myeloid derived suppressor cells (MDSC)/cytokines/urinary catecholamine and perceived stress scale (PSS) with efficacy (ORR, PFS, OS) in melanoma patients treated with pembrolizumab and propranolol.
OUTLINE: This is a phase Ib, dose-escalation study of propranolol hydrochloride followed by a phase II study.
Patients receive propranolol hydrochloride orally (PO) twice daily (BID) and pembrolizumab intravenously (IV) over 30 minutes of day 1. Courses repeat every 3 weeks 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, every 3 months for 6 months, and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib/II Study of Propranolol With Fixed-Dose Pembrolizumab in Patients With Unresectable Stage III and Stage IV Melanoma|
|Actual Study Start Date :||January 31, 2018|
|Estimated Primary Completion Date :||October 11, 2019|
|Estimated Study Completion Date :||October 11, 2020|
Experimental: Treatment (propranolol hydrochloride, pembrolizumab)
Patients receive propranolol hydrochloride PO BID and pembrolizumab IV over 30 minutes of day 1. Courses repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Drug: Propranolol Hydrochloride
- Dose limiting toxicities (DLT) defined as any grade 3 or higher hematological or non-hematological toxicity that is probably or definitely related to treatment according to Common Terminology Criteria for Adverse Events version 4.03 (Phase Ib) [ Time Frame: Up to 12 weeks ]Adverse events and toxicities will be summarized by dose level using frequencies and relative frequencies.
- Overall response rate (ORR) per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) version 1.1 (Phase II) [ Time Frame: Up to 6 months ]ORR is defined as partial or complete response within 6 months of initiating combination therapy.
- Overall survival (OS) (Phase II) [ Time Frame: From treatment initiation until death due to any cause (event) or last follow-up, assessed up to 2 years ]Will be summarized using standard Kaplan-Meier methods and rates will be obtained with 90% confidence intervals.
- PFS (Phase II) [ Time Frame: From treatment initiation until disease progression, death due to disease (events), or last follow-up, assessed up to 2 years ]Will summarized using standard Kaplan-Meier methods and rates will be obtained with 90% confidence intervals.
- Progression free survival (PFS) (Phase II) [ Time Frame: At 1 year ]Will be summarized using standard Kaplan-Meier methods and rates will be obtained with 90% confidence intervals.
- Changes in the levels of biomarkers [ Time Frame: Baseline up to 2 years ]to correlate baseline or changes in levels of biomarkers with efficacy in melanoma patients treated with pembrolizumab and propranolol.
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): NCT03384836
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Shipra Gandhi 716-845-2544 Shipra.Gandhi@roswellpark.org|
|Principal Investigator: Shipra Gandhi|
|Principal Investigator:||Shipra Gandhi, MD||Roswell Park Cancer Institute|