- ICH GCP
- US Clinical Trials Registry
- Clinical Trial 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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Mustafa Khasraw, MBChB, MD, FRCP, FRACP
- Phone Number: 9196845301
- Email: dukebrain1@dm.duke.edu
Study Contact Backup
- Name: Erin Severance, BA
- Phone Number: 9196845301
- Email: dukebrain1@dm.duke.edu
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Recruiting
- Duke University Medical Center
-
Contact:
- Mustafa Khasraw, MBChB, MD, FRCP, FRACP
- Phone Number: 9196845301
- Email: dukebrain1@dm.duke.edu
-
Contact:
- Erin Severance, BA
- Phone Number: 9196845301
- Email: dukebrain1@dm.duke.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
- 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.
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single dose of evolocumab
420 mg of evolocumab subcutaneous injection 7-14 days before scheduled surgery for malignant glioma
|
Evolocumab subcutaneous injection
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence of evolocumab in surgical tumor tissue and tissue from a matched control group
Time Frame: At time of surgical resection
|
Determined by mass spectrometry
|
At time of surgical resection
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Level of lipid metabolism within the surgical tumor tissue and tissue from a matched control group
Time Frame: At time of surgical resection
|
Determined by fluorescence-activated cell sorting (FACS)
|
At time of surgical resection
|
Major histocompatibility complex-1 (MHC-I) expression within the surgical tumor tissue and tissue from a matched control group
Time Frame: At time of surgical resection
|
Determined by FACS
|
At time of surgical resection
|
Correlation between serum and surgical tumor tissue levels of evolocumab
Time Frame: 2 weeks
|
Using serum taken before receiving evolocumab (7-14 days before surgery) and serum taken at the time of surgery
|
2 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mustafa Khasraw, MBChB, MD, FRCP, FRACP, Duke University
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Glioma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Serine Proteinase Inhibitors
- PCSK9 Inhibitors
- Evolocumab
Other Study ID Numbers
- Pro00108375
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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