AzTrials
AzTrials

GliomaPhase 1NCT05413304

Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis

A Phase 1 study testing Pre-operative abemaciclib, Device for Cerebral Fluid Dialysate Collection and Ashion Analytics GEM ExTra in people with Glioma, run by National Cancer Institute (NCI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Background: Diffuse midline gliomas are the most aggressive brain tumors of childhood and young adults. Most people with these tumors survive less than 2 years. Researchers want to see if an anticancer drug (abemaciclib) can help. Read more about this study

Who is it for?
Ages 18 to 39 years
Conditions the study is for
Glioma
What is being tested?
Pre-operative abemaciclib, Device for Cerebral Fluid Dialysate Collection and Ashion Analytics GEM ExTra
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
7 Apr 2023to 1 Sep 2027
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 39 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Participants must have recurrent high-grade glioma or midline glioma based on clinical and/or radiologic findings
  • Participants with cortical high-grade gliomas must have previous intra-operative pathology confirming disease
  • Participants must be >= 18 and <= 39 years old at the time of enrollment
  • Ability to swallow tablets/pills
  • Prior Therapies:
  • At least 4 weeks must have elapsed since any major surgeries, with no evidence of infections. Minimally invasive biopsies (outside of the brainstem) and central line placements are not considered major surgeries
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  • Participants who have received prior treatment with abemaciclib or another specific cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor are not eligible for enrollment (ex., Ribociclib, Palbociclib - list is not all inclusive)
  • Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade <=1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to treatment. A washout period of at least 14 days or 4 half-lives from last disease directed therapy, whichever is shorter, is required between last chemotherapy dose and treatment.
  • Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and treatment.
  • Adequate performance scale as defined below:
  • Karnofsky >=50% within 14 days prior to enrollment.
  • Adequate organ function within 14 days prior to enrollment as defined below:
  • Hematologic Function: Participants must have an absolute neutrophil count >=1500/microliters, hemoglobin >=9 g/dL (transfusion independent, defined as not receiving blood transfusion unless related to trauma or surgeries), and platelets >=100,000/microliters (transfusion independent, defined as not receiving platelet transfusions unless related to trauma or surgeries)
  • Hepatic Function: Participants must have bilirubin within 1.5 x the upper limit of normal for age, with the exception of those with Gilbert syndrome, and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) within < 3 x upper limit of normal.
  • Renal Function: Participants must have a creatinine clearance or radioisotope glomerular filtration rate (GFR) >60ml/min/1.73 m^2 or a normal serum creatinine.
  • Cardiac Function: Normal ejection fraction (echocardiogram (ECHO) or cardiac magnetic resonance imaging (MRI) >= 53% (or the institutional normal); Corrected QT (QTC) or Fridericia's corrected QT (QTcF) < 450 msec.
  • Willingness to avoid grapefruit or grapefruit juice during abemaciclib administration
  • Informed Consent: Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
  • Willingness of participant or LAR to sign a written informed consent document and co-enroll in study 03-N-0164
  • The effects of abemaciclib on the developing human fetus are unknown, however cyclin-dependent kinase (CDK)-inhibiting agents are known to be teratogenic. Temozolomide is a cytotoxic chemotherapeutic agent which is known to be teratogenic. For these reasons, women of child-bearing potential must agree to use a highly effective method of contraception prior to study entry, for the duration of study participation, and for 3 weeks after the last dose of abemaciclib and 6 months after temozolomide. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation.
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Woman participants of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 7 days of the first dose of abemaciclib.
  • Highly effective contraception includes intrauterine devices (IUD), hormonal (birth control pills, injections, implants), tubal ligation, or partners vasectomy.
  • --Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a participant or spouse/partner is determined to be pregnant following abemaciclib initiation she must discontinue treatment immediately. Data on fetal outcomes and breastfeeding are to be collected for regulatory reporting and drug safety evaluation.
  • -Abemaciclib administration must be able to begin no later than 14 days after the date of radiographic diagnosis (by T2 or FLAIR imaging)

Who cannot join

  • Participants who cannot safely undergo a biopsy due to contraindications
  • Pregnant women, or women who intent to become pregnant during the study, are excluded from this study because of the teratogenic effects of abemaciclib. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study.
  • Serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel that would preclude adequate absorption, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active bleeding diatheses or renal transplant, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
  • Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Participants with HIV who have adequate cluster of differentiation 4 (CD4) counts and who have no requirement for antiviral therapy will be eligible. NOTE: Screening is not required for enrollment.
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  • Requires treatment with strong/moderate cytochrome P450, family 3, subfamily A. (CYP3A) inhibitors or inducers. Participants receiving any medications or substances that are inducers or strong/moderate inhibitors of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
  • Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol (see Study Procedure Manual). Prosthesis or orthopedic or dental braces that would interfere with MRI.
  • Refractory nausea and vomiting that would limit drug administration in the opinion of the Principal Investigator
  • Known severe hypersensitivity to abemaciclib, temozolomide or any excipient of abemaciclib or temozolomide or history of allergic reactions attributed to compounds of similar chemical or biologic composition to abemaciclib and temozolomide.
  • Clinical judgment by the investigator that the participant should not participate in the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Feasibility of Evaluating Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis

Background:

Diffuse midline gliomas are the most aggressive brain tumors of childhood and young adults. Most people with these tumors survive less than 2 years. Researchers want to see if an anticancer drug (abemaciclib) can help.

Read more

Objective:

To see if researchers can measure how much abemaciclib is in a person's brain tumor and brain fluid after they take the drug for a few days.

Eligibility:

People aged 18 to 39 with recurrent high-grade glioma or diffuse midline glioma.

Design:

Participants will be screened with:

Medical history

Physical exam

Blood and urine tests

Tests of heart function

Imaging scans of the brain, with a contrast agent

Screening tests will be repeated during the study. Participants will also have chest X-rays.

Participants will take abemaciclib by mouth twice a day for 4 and a half days.

Participants will undergo surgery. They will have either a tumor biopsy (a needle will be inserted to remove a small piece of tissue) or a surgical resection (part or all of the tumor will be removed). A small tube (catheter) will be placed in their brain for 48 hours to collect fluid samples. They will have a neurological exam every few hours while the tube is in place. Two days later, the tube will be removed without surgery. Participants will stay in the hospital for about 4 days for treatment.

Based on the results of abemaciclib levels in the brain, participants may keep taking abemaciclib and another drug (temozolomide) by mouth until their cancer gets worse or they have bad side effects. While taking these two drugs, participants will come back to the clinic for follow-up routinely. They will be followed by the study for life....

Read the detailed description

Background

Diffuse midline gliomas are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates of <10%. These tumors are infiltrative midline high-grade gliomas. Treatment failure is due in part to the presence of the blood-brain barrier (BBB), which limits permeability of varied agents.

Efforts to evaluate drug delivery across the BBB in midline gliomas have been restricted to post biopsy specimens. In comparison, intracerebral microdialysis sampling of cortical tissue has been shown to be a highly effective tool in determining cortical neuropharmacokinetics (brain extracellular fluid penetration, accumulation and excretion) intratumorally and peritumorally in adult brain tumor participants. Microdialysis is underutilized in the adult brain tumor setting to evaluate chemotherapy or targeted therapy permeability.

Within the United States (US), midline gliomas are not routinely biopsied. However, in the last several years, using modern surgical techniques, biopsy at the time of diagnosis has been performed with acceptable risks (4% mortality rate), with a feasible means to molecularly characterize the tumors; in order to identify potentially druggable targets.

One of the main attributes of disease progression/proliferation in midline gliomas is associated with dysregulation of the cell cycle. Cyclin-dependent kinase inhibitor 2A (CDKN2A) is the primary inhibitory brake on cyclin-dependent kinase 4 and 6 (CDK4/6) driven signaling and is commonly deleted in glioblastoma, pancreas, bladder, breast and prostate cancer. The specific CDK4/6 inhibitor, abemaciclib, has Food and Drug Administration (FDA) approval for the treatment of metastatic breast cancer.

This is a safety and feasibility study to evaluate pharmacokinetic and pharmacodynamic effects post abemaciclib administration in recurrent high grade glioma participants (cortical and midline tumors). We propose a trial using clinical microdialysis, placed in diffuse midline glioma tissue post biopsy, as an experimental research tool, to assess central nervous system (CNS) drug entry and targeted inhibition with abemaciclib. These studies are focused with the overall intent to inform future clinical therapies and preclinical modeling.

Objectives:

To evaluate safety and feasibility of intratumoral microdialysis placement post high grade glioma resection or midline glioma biopsy

To evaluate safety and feasibility of brain interstitial dialysate sampling in glioma participants post abemaciclib administration

To measure intratumoral vs. systemic concentrations of abemaciclib in glioma participants post abemaciclib administration

Eligibility:

Participants must have recurrent high-grade glioma or diffuse midline glioma based on clinical and/or radiologic findings

Participants with cortical high-grade gliomas must have previous intra-operative pathology confirming disease

Participants must be =>18 and <= 39 years of age, at time of enrollment

Ability to swallow tablets/pills

Must have adequate organ function as per laboratory testing parameters

Abemaciclib administration must be able to begin no later than 14 days after the date of radiographic diagnosis (by T2 or fluid-attenuated inversion recovery (FLAIR) imaging)

Design:

This is a safety and feasibility study to evaluate tumor pharmacokinetics (PK) and pharmacodynamics (PD) of abemaciclib in recurrent high-grade glioma and midline glioma participants in need of surgical resection or biopsy, respectively.

All participants will take abemaciclib pre-operatively for 4.5 days (9 total doses of abemaciclib) at twice daily dosing.

A maximally safe surgical resection for cortical high-grade glioma or stereotactic needle biopsy for midline glioma will be performed in the operating room (OR). Microdialysis insertion (based on participant safety and surgical feasibility) will be performed post-biopsy in the OR and placement will be verified by brain computed tomography (CT).

Continuous microdialysis sampling will be obtained over the course of the next 48 hours, with subsequent removal of the catheter at the bedside.

After discharge from National Institutes of Health (NIH) inpatient, PK and PD findings will assist in determination of whether the participant will continue to receive abemaciclib therapy. If intratumoral or PK brain dialysate sampling concentrations are >10nmol/L, or PD findings suggest cyclin-dependent kinase (CDK) inhibition (decreased expression of Retinoblastoma protein (Rb) and/or topoisomerase II (topoII), then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy post resection or biopsy.

Maintenance therapy will be abemaciclib 150mg po twice a day (BID) x 28 days together with temozolomide 200mg/m^2 po daily x 5 days in 28-day cycles (temozolomide 150mg/m^2 po daily x 5 days for cycle 1). After every 3 cycles, repeat brain magnetic resonance imaging's (MRIs) will be obtained to evaluate treatment response and disease progression.

If a participant starts to exhibit signs of clinical deterioration or radiographic progression, the participant will discontinue maintenance therapy, with ongoing contact for survival approximately every 6 months (+/- 14 days) until death.

Results of the PK measurements and molecular testing will be provided to the participant's home oncologist to provide for assistance with directed therapy decisions (outside of this investigational trial).

We propose to evaluate 5 participants. The accrual ceiling will be set at 17 participants to account for screen failures and inevaluable participants.

Conditions
Glioma
Being tested
Pre-operative abemaciclib, Device for Cerebral Fluid Dialysate Collection, Ashion Analytics GEM ExTra, abemaciclib + temozolomide, Temozolomide
Keywords
Central Nervous System, Cdk4/6, Brain Cancer, Surgical Resection
Medical subject headings
Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pre-operative abemaciclibDrug

    Also called Verzenio

    Pre-operatively for 4.5 days; 200mg twice daily (9 total doses)

  • Device for Cerebral Fluid Dialysate CollectionDevice

    Post-resection or post-biopsy continuous intracerebral microdialysis sampling for 48 hours to assess central nervous system (CNS) drug entry and targeted inhibition with abemaciclib

  • Ashion Analytics GEM ExTraDevice

    Also called Ashion Analytics Genomic Enabled Medicine Exome and Transcriptome

    Resection/biopsy genomic sampling of tumor tissue and blood to identify therapeutic targets

  • abemaciclib + temozolomideDrug

    Also called Verzenio + Temodar

    Abemaciclib 150mg by mouth (po) twice a day (BID) and temozolomide 200mg/m^2 po daily x 5 days in 28-day cycles (temozolomide 150mg/m^2 po daily x 5 days for cycle 1)

  • TemozolomideDrug

    Also called Temodar

    Temozolomide 150mg/m^2 by mouth (po) daily x 5 days for cycle 1

  • Brain MRIDiagnostic test

    Also called Brain magnetic resonance imaging

    Screening (within 14 days prior to enrollment), baseline (within 14 days of first dose), as clinically indicated at catheter removal Day 7 (>48 hours post op), maintenance therapy (after every 3 cycles), and post treatment (safety and long-term follow-up) as clinically indicated.

  • Brain CTDiagnostic test

    Also called Brain computed tomography

    Microdialysis (catheter in place) Day 5 and Day 6, and as clinically indicated at catheter removal Day 7 (>48 hours post op).

  • EKGDiagnostic test

    Also called Electrocardiogram

    Screening (within 14 days prior to enrollment), baseline (within 14 days of first dose), and as clinically indicated at catheter removal Day 7 (>48 hours post op).

  • Chest X-rayDiagnostic test

    Also called CXR

    Baseline (within 14 days of first dose), and as clinically indicated at catheter removal Day 7 (>48 hours post op).

  • Biopsy/resectionProcedure or surgery

    Also called Bx/resection

    Microdialysis (catheter in place) Day 5 and Day 6.

Study groups in NCT05413304
Study groupRoleWhat they receive
Arm 1/Cohort 1/ Abemaciclib and Microdialysis MonitoringExperimentalAbemaciclib orally twice a day (BID) for 4.5 days followed by resection or biopsy and microdialysis catheter placement with continuous monitoring for 48 hours post-operative and genomic sampling of tissue/blood; followed by Arm 2/abemaciclib + temozolomide maintenance therapy.
Receives: Drug: Pre-operative abemaciclib; Device: Device for Cerebral Fluid Dialysate Collection; Device: Ashion Analytics GEM ExTra; Drug: abemaciclib + temozolomide; Drug: Temozolomide; Diagnostic Test: Brain MRI; Diagnostic Test: Brain CT; Diagnostic Test: EKG; Diagnostic Test: Chest X-ray; Procedure: Biopsy/resection
Arm 2/Cohort 2/Abemaciclib + Temozolomide Maintenance TherapyExperimentalMaintenance therapy is abemaciclib 150mg by mouth (PO) BID x 28 days + temozolomide 200mg/m^2 PO daily x 5 days in 28-day cycles (temozolomide 150mg/m^2 PO daily x 5 days for cycle 1).
Receives: Drug: Pre-operative abemaciclib; Device: Device for Cerebral Fluid Dialysate Collection; Device: Ashion Analytics GEM ExTra; Drug: abemaciclib + temozolomide; Drug: Temozolomide; Diagnostic Test: Brain MRI; Diagnostic Test: Brain CT; Diagnostic Test: EKG; Diagnostic Test: Chest X-ray; Procedure: Biopsy/resection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Have Adequate Intra-tumoral Sampling Reported With an 80% Confidence Interval

    The percentage of participants who have adequate intra-tumoral sampling was determined and reported with an 80% confidence interval. Adequate intra-tumoral tissue concentration is <10nmol/L. Intra-tumoral sampling was performed by microdialysis.

    Measured: At surgery (less than 14 hours from surgery), biopsy (after 4 days of abemaciclib), and 2, 6, 10, 14, 18, 22, 26, 30, 34, 38,40, 44, and 48 hours post catheter insertion

  2. Percentage of Participants Who Have Adequate Intra-tumoral Sampling Reported With a 95% Confidence Interval

    The percentage of participants who have adequate intra-tumoral sampling was determined and reported with a 95% confidence interval. Adequate intra-tumoral tissue concentration is <10nmol/L. Intra-tumoral sampling was performed by microdialysis.

    Measured: At surgery (less than 14 hours from surgery), biopsy (after 4 days of abemaciclib), and 2, 6, 10, 14, 18, 22, 26, 30, 34, 38,40, 44, and 48 hours post catheter insertion

  3. Number of Participants Who Experience Any Type Grade 1, 2, 3, 4, and/or 5 Adverse Event (AE)/Complication Possibly, Probably, and/or Definitely Related to Adverse Events for Participants (pt) Receiving Abemaciclib

    AEs were assessed by the Common Terminology Criteria for Adverse Events v5.0. A non-serious AE is any untoward medical occurrence. A serious AE is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the pt or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1:mild. Grade 2: moderate. Grade 3: severe. Grade 4: life-threatening. Grade 5: death related to adverse event. All participants who receive at least 1 dose of abemaciclib or undergo the procedure to place the catheter will have their safety information reported. This table is related to AEs from abemaciclib therapy(pre-surgery). Values in the table will and should be different than other AE tables based on toleration of therapy at varied times for each pt.

    Measured: Study Day 1 through 30 days after the last intervention through study completion, an average of 4.5 months

  4. Number of Grade 1, 2, 3, 4, and/or 5 Adverse Events (AE) At Least Possibly Related Adverse Events for Participants(pt) Receiving Combination Therapy With Abemaciclib and Temozolomide

    AEs were assessed by the Common Terminology Criteria for AEs (CTCAE v5.0). A non-serious AE is any untoward medical occurrence. A serious AE is an adverse event or suspected adverse reaction that results in death, life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1: mild. Grade 2: moderate. Grade 3: severe. Grade: 4 life-threatening. Grade 5: death related to AE. All participants who receive at least 1 dose of abemaciclib or undergo the procedure to place the catheter are reported. This table is related to AEs from abemaciclib post-surgery,given during maintenance cycle with temozolomide. Values in the table will and should be different than other AE tables based on toleration of therapy at varied times for each pt.

    Measured: Study Day 1 through 30 days after the last intervention through study completion, an average of 4.5 months

Secondary outcomes (11)

  1. Time to Maximum Observed Plasma Concentration an Hour (Tmax(hr) of Drug Abemaciclib

    Blood samples were collected to determine the time to maximum observed plasma concentration an hour (Tmax(hr) of drug abemaciclib. Abemaciclib levels in plasma were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

  2. Maximum Plasma Concentration (Cmax) of Drug Abemaciclib

    Blood samples were collected to determine the maximum plasma concentration of drug abemaciclib. Abemaciclib levels in plasma were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

  3. Area Under the Plasma Concentration (AUC) of Drug Abemaciclib

    AUC is a measure of the drug plasma serum concentration of abemaciclib over time. It is used to characterize drug absorption. Abemaciclib levels in plasma were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

  4. Maximum Plasma Concentration (Cmax) of Unbound Abemaciclib

    Unbound abemaciclib plasma exposure was calculated by the total drug exposure multiplied by the mean unbound fraction (fu,0.06) in human plasma.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

  5. Area Under the Plasma Concentration (AUC) of Unbound Abemaciclib

    AUC is a measure of the total drug plasma serum concentration of abemaciclib over time. It is used to characterize drug absorption. Unbound abemaciclib plasma exposure was calculated by the total drug exposure multiplied by the mean unbound fraction (fu,0.06) in human plasma.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

  6. Time to Maximum Observed Plasma Concentration an Hour (Tmax(hr) of Brain Dialysate

    Urea concentrations in blood and brain interstitial fluid were measured at timed intervals. Abemaciclib levels in plasma, brain tissue and dialysate were measured and compared by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis to determine plasma concentration.

    Measured: Approximately 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 40, 44, and 48 hours post catheter insertion

  7. Maximum Plasma Concentration (Cmax) of Brain Dialysate

    Blood and brain interstitial fluid were obtained via microdialysis catheter in the brain and urea (metabolite) concentrations in blood and brain interstitial fluid were measured at timed intervals. Abemaciclib levels in plasma, brain tissue and dialysate were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) to determine plasma concentration of drug in the brain.

    Measured: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 40, 44, and 48 hours post catheter insertion

  8. Area Under the Plasma Concentration (AUC) of Brain Dialysate

    AUC is a measure of the total drug plasma serum concentration of abemaciclib over time. Blood and brain interstitial fluid were obtained via microdialysis catheter in the brain and urea (metabolite) concentrations in blood and brain interstitial fluid were measured at timed intervals. Abemaciclib levels in plasma, brain tissue and dialysate were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis to determine concentration of drug in the brain.

    Measured: Approximately 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 40, 44, and 48 hours post catheter insertion

  9. Concentration of Total Drug Abemaciclib From Tissue Obtained Via Brain Biopsy

    Biopsied tumor tissue was obtained using a stereotactic needle in the brain. A minimum of 6 samples were taken and analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) to determine drug concentrations in the brain tissue.

    Measured: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 40, 44, and 48 hours post catheter insertion

  10. Brain Biopsy Sampling Time

    Brain biopsy sampling time is the timing of when the tumor tissue was biopsied since the last dose of abemaciclib.

    Measured: 2, 6, 10, 14, 18, 22, 26, 30, 34, 38, 40, 44, and 48 hours post catheter insertion

  11. Ratio of Area Under the Plasma Concentration (AUC) in Brain Dialysate to Unbound Drug Abemaciclib AUC in Plasma

    AUC is a measure of the total drug plasma serum concentration of abemaciclib over time. Unbound abemaciclib plasma exposure was calculated by the total drug exposure multiplied by the mean unbound fraction (fu,0.06) in human plasma. Abemaciclib levels in plasma, brain tissue and dialysate were measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) analysis.

    Measured: Approximately 5, 6, 10, 12, 14, 28, 52, 76 hours after last dose of abemaciclib

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2022
  2. Study start7 Apr 2023
  3. Primary completion21 Oct 2025
  4. Study completion1 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05413304
Sponsor's protocol ID
220003
Other IDs
22-C-0003
Status last verified
Sep 2026
First submitted
9 Jun 2022
Last updated
6 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Publications

  • Nduom EK, Glod J, Brown DA, Fagan M, Dalmage M, Heiss J, Steinberg SM, Peer C, Figg WD, Jackson S. Clinical protocol: Feasibility of evaluating abemaciclib neuropharmacokinetics of diffuse midline glioma using intratumoral microdialysis. PLoS One. 2023 Sep 8;18(9):e0291068. doi: 10.1371/journal.pone.0291068. eCollection 2023.

    PubMed 37682953

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pre-operative abemaciclib, Device for Cerebral Fluid Dialysate Collection and Ashion Analytics GEM ExTra in people with Glioma, run by National Cancer Institute (NCI) 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 25 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. 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?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants Who Have Adequate Intra-tumoral Sampling Reported With an 80% Confidence Interval (time frame: At surgery (less than 14 hours from surgery), biopsy (after 4 days of abemaciclib), and 2, 6, 10, 14, 18, 22, 26, 30, 34, 38,40, 44, and 48 hours post catheter insertion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05413304, which also lists 1 linked publication.

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 6 Oct 2026.

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