Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis

NCT05413304 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 22000322-C-0003
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

Glioma

Keywords

Central Nervous System; Cdk4/6; Brain Cancer; Surgical Resection

Outcome Measures

Primary Outcomes (3)

• intra-tumoral sampling adequacy

  fraction of participants who have adequate intra-tumoral sampling

  surgery/biopsy and multiple timed retrievals 2 - 48 hours post catheter insertion

• concentration of abemaciclib

  intratumoral vs. systemic concentrations of abemaciclib post abemaciclib administration.

  intratumoral: surgery/biopsy and multiple timed retrievals 2 - 48 hours post catheter insertion; blood/systemic: surgery/biopsy, multiple timed retrievals 1-72 hours post catheter insertion, and Day 5 of every other maintenance therapy cycle

• adverse events

  fraction of participants who experience any adverse event/complication, including adverse events grades and types

  Study Day 1 through 30 days after the last intervention

Secondary Outcomes (1)

• relationship between abemaciclib PK and PD studies on subsequent treatment and participant outcome

  10 years post-enrollment

Study Arms (1)

1/Abemaciclib and microdialysis monitoring

EXPERIMENTAL

Abemaciclib orally 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 abemaciclib+temozolomide maintenance therapy

Drug: pre-operative abemaciclib; Device: Device for Cerebral Fluid Dialysate Collection; Device: Ashion Analytics GEM ExTra; Drug: abemaciclib + temozolomide

Interventions

pre-operative abemaciclib DRUG

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

1/Abemaciclib and microdialysis monitoring

Device for Cerebral Fluid Dialysate Collection DEVICE

post-resection or post-biopsy continuous intracerebral microdialysis sampling for 48-hours to assess CNS drug entry and targeted inhibition with abemaciclib

1/Abemaciclib and microdialysis monitoring

Ashion Analytics GEM ExTra DEVICE

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

1/Abemaciclib and microdialysis monitoring

abemaciclib + temozolomide DRUG

abemaciclib 150mg po BID and temozolomide 200mg/m2 po daily x 5 days in 28 day cycles (temozolomide 150mg/m2 po daily x 5 days for cycle 1)

1/Abemaciclib and microdialysis monitoring

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Participants who have received prior treatment with abemaciclib or another specific 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 AST/ALT within \< 3 x upper limit of normal.
• Renal Function: Participants must have a creatinine clearance or radioisotope GFR \>60ml/min/1.73 m2 or a normal serum creatinine.

You may not qualify if:

• 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 CD4 counts and who have no requirement for antiviral therapy will be eligible. NOTE: Screening is not required for enrollment.
• Requires treatment with strong/moderate 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 37682953 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioma; Brain Neoplasms

Interventions

abemaciclib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Sadhana Jackson, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2022
• First Posted: June 10, 2022
• Study Start: April 7, 2023
• Primary Completion: October 21, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-02-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@Genomic data will be shared from the time of upload to dbGaP.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI ETCTN Director in conjunction with the NCI/DCTD Regulatory Affairs Branch). @@@@@@Genomic IPD will be shared through dbGaP, per rules of the database, for purposes of genomic analysis.

Locations

US (1)