NCT04937413

The PCSK9i Inhibitor Evolocumab - a Surgical Trial of Pharamcodynamics and Kinetics Evaluation

PEskE: A Phase 0/Surgical Window-of-opportunity Study to Evaluate the Pharmacokinetics and Pharmacodynamics of Evolocumab in Patients With Recurrent High-grade Glioma or Glioblastoma

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Duke University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase 0 surgical window of opportunity trial seeks to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an FDA-approved proprotein convertase/ kexin type 9 serine protease inhibitor (PCSK9i) in patients with primary and recurrent World Health Organization (WHO) grade IV malignant glioma. The investigators intend to evaluate whether a clinically licensed PCSK9i called evolocumab (also known as Repatha) can be repurposed as a potential immunotherapeutic for high grade glioma by testing its ability to access the intracranial space. The primary objective is to evaluate whether evolocumab crosses the blood brain barrier (BBB) and is measurable in the resected tumor specimens of patients with primary and recurrent high grade glioma or glioblastoma.

Detailed description

A maximum of 10 participants will receive 420 mg (the maximum single dose) of evolocumab subcutaneously into their thigh, abdomen or upper arm 7-14 days prior to surgical de-bulking of their tumor. After de-bulking, leftover tissue not required for histological analysis will be collected, and the level of evolocumab will be quantified. At two time points, prior to injection of evolocumab and at time of their surgery, participants will have peripheral blood drawn to analyze serum levels of the drug (for comparison to levels found in their leftover tissue). The investigators will follow-up with participants about 2 weeks after surgery at their post-operative visit. A matched cohort of resected tumor specimens from patients who were not treated with evolocumab from the Duke Brain Tumor Center Biorepository will be used as a comparison for the primary objective and 2 of the 3 secondary objectives of this study comparing brain tumor tissue specimens of patients who did and did not receive evolocumab with respect to lipid metabolism and tumor cells expressing MHC-I.

Conditions

• Malignant Glioma
• Glioblastoma

Interventions

Type	Name	Description
DRUG	Evolocumab	Evolocumab subcutaneous injection

Timeline

• Start date: 2021-10-08
• Primary completion: 2023-09-13
• Completion: 2023-10-12
• First posted: 2021-06-24
• Last updated: 2024-06-25

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study