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

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Treatments: Evolocumab

Criteria

Inclusion Criteria:

• 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:

1. Hemoglobin ≥ 10 g/dl (Note: the use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable)

2. Leukocytes ≥ 1,500/mm3

3. Absolute Neutrophil Count (ANC) ≥ 1,000/mm3

4. 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:

1. 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.)

2. AST(SGOT) and ALT(SGPT) ≥ 1.5 × ULN

• Negative serum pregnancy test (in females of childbearing potential) within 48 hours of starting evolocumab.

Exclusion Criteria:

• Any patient with a history of a serious hypersensitivity reaction to evolocumab or any of the excipients in evolocumab

• Patients with severe hepatic impairment outside of the range defined in the inclusion criteria within 7 days of starting 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.