Malignant GliomaEarly Phase 1NCT04937413
The PCSK9i Inhibitor Evolocumab - a Surgical Trial of Pharamcodynamics and Kinetics Evaluation
A Early Phase 1 study testing Evolocumab in people with Malignant Glioma and Glioblastoma, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2021to 12 Oct 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: 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
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.
Read the 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
- Being tested
- Evolocumab
- Keywords
- Pro00108375, Khasraw, PCSK9i, Evolocumab, Glioma, Glioblastoma, PEskE
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabDrug
Also called Repatha
Evolocumab subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Single dose of evolocumab | Experimental | 420 mg of evolocumab subcutaneous injection 7-14 days before scheduled surgery for malignant glioma Receives: Drug: Evolocumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of evolocumab in surgical tumor tissue and tissue from a matched control group
Determined by mass spectrometry
Measured: At time of surgical resection
Secondary outcomes (3)
Level of lipid metabolism within the surgical tumor tissue and tissue from a matched control group
Determined by fluorescence-activated cell sorting (FACS)
Measured: At time of surgical resection
Major histocompatibility complex-1 (MHC-I) expression within the surgical tumor tissue and tissue from a matched control group
Determined by FACS
Measured: At time of surgical resection
Correlation between serum and surgical tumor tissue levels of evolocumab
Using serum taken before receiving evolocumab (7-14 days before surgery) and serum taken at the time of surgery
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2021
- Study start8 Oct 2021
- Primary completion13 Sep 2023
- Study completion12 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mustafa Khasraw, MBChB, MD, FRCP, FRACP, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04937413
- Sponsor's protocol ID
- Pro00108375
- Status last verified
- May 2024
- First submitted
- 16 Jun 2021
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04937413
- Acronym / sponsor ID
- Pro00108375
- Conditions
- Malignant Glioma, Glioblastoma
- Keywords
- Pro00108375, Khasraw, PCSK9i, Evolocumab, Glioma, Glioblastoma, PEskE
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- 8 Oct 2021 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 12 Oct 2023 (actual)
- First posted
- 24 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single dose of evolocumab | Experimental | Drug: Evolocumab420 mg of evolocumab subcutaneous injection 7-14 days before scheduled surgery for malignant glioma |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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:
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: RepathaEvolocumab subcutaneous injection | Drug | Single dose of evolocumab |
Primary outcome
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
3 secondary outcomes
Level of lipid metabolism within the surgical tumor tissue and tissue from a matched control group
Time frame: 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
Correlation between serum and surgical tumor tissue levels of evolocumab
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- The Preston Robert Tisch Brain Tumor Center at DukeLink provided by the sponsor.
- Duke HealthLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mustafa Khasraw, MBChB, MD, FRCP, FRACP principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Evolocumab in people with Malignant Glioma and Glioblastoma, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of evolocumab in surgical tumor tissue and tissue from a matched control group (time frame: At time of surgical resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.