Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Arrhythmia Agents

Antihypertensive Agents

Vasodilator Agents

Immune Checkpoint Inhibitors

Pembrolizumab

Propranolol

Adrenergic beta-Antagonists

Adrenergic Agents

Adrenergic Antagonists

Antineoplastic Agents, Immunological

Neurotransmitter Agents

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.

Laboratory Biomarker Analysis

Propranolol Hydrochloride

Melinda Yushak, MD

Shipra Gandhi

Pauline Funchain, MD

Natalie East, RN, BSN

Joseph Drabick, MD

Shipra Gandhi, MD

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. Pembrolizumab is a monoclonal antibody that "takes the brakes off the immune system" and thus allows for anti-tumor immune responses. 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.

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 OBJECTIVES:

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).

TERTIARY OBJECTIVES:

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.

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

A Phase Ib/II Study of Propranolol With Fixed-Dose Pembrolizumab in Patients With Unresectable Stage III and Stage IV Melanoma

to correlate baseline or changes in levels of biomarkers with efficacy in melanoma patients treated with pembrolizumab and propranolol.

Adverse events and toxicities will be summarized by dose level using frequencies and relative frequencies.

ORR is defined as partial or complete response within 6 months of initiating combination therapy.

Will be summarized using standard Kaplan-Meier methods and rates will be obtained with 90% confidence intervals.

Will summarized using standard Kaplan-Meier methods and rates will be obtained with 90% confidence intervals.

Roswell Park Cancer Institute

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery	NCT03384836	Stage IIIC Cuta... Stage IV Cutane...	Laboratory Biom... Pembrolizumab Propranolol Hyd...	18 Years -	Roswell Park Cancer Institute
Propranolol Hydrochloride and Pembrolizumab in Treating Patients With Stage IIIC-IV Melanoma That Cannot Be Removed by Surgery	NCT03384836	Stage IIIC Cuta... Stage IV Cutane...	Laboratory Biom... Pembrolizumab Propranolol Hyd...	18 Years -	Roswell Park Cancer Institute

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