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

Status
Active
Cancer Type
Melanoma
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT03384836
Protocol IDs
I 53217 (primary)
NCI-2017-02210
Study Sponsor
Roswell Park Cancer Institute

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.

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

Eligibility

  1. Participants must be newly diagnosed, treatment-naive with histologically confirmed stage IIIC unresectable melanoma or stage IV melanoma
  2. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  3. Available archival formalin-fixed paraffin-embedded (FFPE) from a prior biopsy or, participant must be willing to have a tissue biopsy taken at a clinic visit prior to start of study treatment
  4. Have measurable disease per RECIST version (v)1.1
  5. Ability to swallow and retain oral medication
  6. Absolute neutrophil count (ANC) >= 1500/uL
  7. Hemoglobin (Hb) >= 9 g/dL
  8. Platelet count >= 100,000/uL, unless patient has Gilbert's syndrome
  9. Total bilirubin =< 1.5 x ULN (upper limit of normal)
  10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x ULN * If the patient has liver disease AST and ALT =< 5 x ULN
  11. Serum or plasma (based on site’s standard operating procedure [SOP]) creatinine < 2 x ULN
  12. Participants of child-bearing potential must have a negative pregnancy test at study entry and then agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  13. Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
**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.
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Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.