Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis
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|ClinicalTrials.gov Identifier: NCT05413304|
Recruitment Status : Not yet recruiting
First Posted : June 10, 2022
Last Update Posted : August 12, 2022
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.
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.
People aged 18 to 39 with recurrent high-grade glioma or diffuse midline glioma.
Participants will be screened with:
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioma||Drug: pre-operative abemaciclib Device: Device for Cerebral Fluid Dialysate Collection Device: Ashion Analytics GEM ExTra Drug: abemaciclib + temozolomide||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Feasibility of Evaluating Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis|
|Estimated Study Start Date :||August 17, 2022|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||August 31, 2024|
Experimental: 1/Abemaciclib and microdialysis monitoring
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
pre-operatively for 4.5 days; 200mg twice daily (9 total doses)
Device: Device for Cerebral Fluid Dialysate Collection
post-resection or post-biopsy continuous intracerebral microdialysis sampling for 48-hours to assess CNS drug entry and targeted inhibition with abemaciclib
Device: Ashion Analytics GEM ExTra
resection/biopsy genomic sampling of tumor tissue and blood to identify therapeutic targets
Drug: abemaciclib + temozolomide
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)
- intra-tumoral sampling adequacy [ Time Frame: surgery/biopsy and multiple timed retrievals 2 - 48 hours post catheter insertion ]fraction of participants who have adequate intra-tumoral sampling
- concentration of abemaciclib [ Time Frame: 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 ]intratumoral vs. systemic concentrations of abemaciclib post abemaciclib administration.
- adverse events [ Time Frame: Study Day 1 through 30 days after the last intervention ]fraction of participants who experience any adverse event/complication, including adverse events grades and types
- relationship between abemaciclib PK and PD studies on subsequent treatment and participant outcome [ Time Frame: 10 years post-enrollment ]Descriptive results from abemaciclib PK and PD studies on subsequent treatment and participant outcomes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05413304
|Contact: Sadhana Jackson, M.D.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Sadhana Jackson, M.D.||National Cancer Institute (NCI)|