Propranolol Hydrochloride and Pembrolizumab in Treating Patients with Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery

Active:	Yes
Cancer Type:	Melanoma	NCT ID:	NCT03384836
Trial Phases:	Phase I Phase II	Protocol IDs:	I 53217 (primary) NCI-2017-02210
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Roswell Park Cancer Institute
NCI Full Details:	http://clinicaltrials.gov/show/NCT03384836

Summary

This phase Ib/II trial studies the side effects and best dose of propranolol hydrochloride when given together with pembrolizumab and how well they work in treating patients with stage IIIC-IV melanoma that cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Propranolol hydrochloride is a beta adrenergic blocking agent that can enhance immune cell responses when under stress. Giving propranolol hydrochloride and pembrolizumab may work better in treating patients with melanoma.

Objectives

PRIMARY OBJECTIVES:
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).

SECONDARY OBJECTIVE:
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).

EXPLORATORY OBJECTIVE:
I. To correlate baseline or changes in the levels of biomarkers, like, peripheral T-cell subsets/myeloid derived suppressor cells (MDSC)/cytokines/ 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. Cycles repeat every 3 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT), magnetic resonance imaging (MRI), and blood sample collection throughout the study and tumor biopsy on study.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 6 months, and then every 6 months thereafter.

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.