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

NCT04937413 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: Pro00108375
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Glioma; Glioblastoma

Keywords

Pro00108375; Khasraw; PCSK9i; Evolocumab; Glioma; Glioblastoma; PEskE

Outcome Measures

Primary Outcomes (1)

• Presence of evolocumab in surgical tumor tissue and tissue from a matched control group

  Determined by mass spectrometry

  At time of surgical resection

Secondary Outcomes (3)

• Level of lipid metabolism within the surgical tumor tissue and tissue from a matched control group

  At time of surgical resection

• Major histocompatibility complex-1 (MHC-I) expression within the surgical tumor tissue and tissue from a matched control group

  At time of surgical resection

• Correlation between serum and surgical tumor tissue levels of evolocumab

  2 weeks

Study Arms (1)

Single dose of evolocumab

EXPERIMENTAL

420 mg of evolocumab subcutaneous injection 7-14 days before scheduled surgery for malignant glioma

Drug: Evolocumab

Interventions

Evolocumab DRUG

Evolocumab subcutaneous injection

Also known as: Repatha

Single dose of evolocumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years old
• Newly diagnosed or recurrent high grade glioma (HGG) or glioblastoma (GBM) (if recurrent, prior pathology report indicating HGG or GBM)
• Adequate hematologic function within 14 days prior to starting evolocumab defined as follows:
• Hemoglobin ≥ 10 g/dl (Note: the use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable)
• Leukocytes ≥ 1,500/mm3
• Absolute Neutrophil Count (ANC) ≥ 1,000/mm3
• Platelets ≥ 100,000/mm3
• Adequate renal function within 14 days prior to starting evolocumab defined as calculated creatinine clearance (CrCL) of ≥ 30 mL/min/1.73m2 by the Cockcroft-Gault formula
• Adequate hepatic function within 14 days prior to starting evolocumab defined as follows:
• Total bilirubin ≥ 1.5 x institutional upper limit of normal (ULN) (Note: Patients with known Gilbert disease without other clinically significant liver abnormalities are not excluded.)
• AST(SGOT) and ALT(SGPT) ≥ 1.5 × ULN
• Negative serum pregnancy test (in females of childbearing potential) within 48 hours of starting evolocumab.

You may not qualify if:

• Any patient with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in evolocumab
• History or evidence of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) not associated with any antitumor surgery within 6 months before enrollment
• Infection requiring intravenous antibiotics that was completed \< 1 week of study enrollment (day 1) with the exemption of prophylactic antibiotics for long line insertion or biopsy
• Females of reproductive potential and males who are unwilling to practice an acceptable method(s) of effective birth control while on study through 1 month (2 half-lives) after receiving the last dose of study drug.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Health

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Study Officials

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 24, 2021
• Study Start: October 8, 2021
• Primary Completion: September 13, 2023
• Study Completion: October 12, 2023
• Last Updated: June 25, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)