RECRUITING

Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis

Conditions

Glioma Central Nervous System Cdk4/6 Brain Cancer Surgical Resection

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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....

Official Title

Feasibility of Evaluating Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis

Quick Facts

Study Start:2023-04-07

Study Completion:2026-08-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05413304

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 39 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 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: * 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 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.	* 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

Inclusion Criteria

Exclusion Criteria

* 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
* 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:
* 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 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.

* 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

Contacts and Locations

Study Contact

Sadhana Jackson, M.D.

CONTACT

(240) 760-6018

sadhana.jackson@nih.gov

Principal Investigator

Sadhana Jackson, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Sadhana Jackson, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-04-07

Study Completion Date2026-08-31

Study Record Updates

Study Start Date2023-04-07

Study Completion Date2026-08-31

Terms related to this study

Keywords Provided by Researchers

Central Nervous System
Cdk4/6
Brain Cancer
Surgical Resection

Additional Relevant MeSH Terms

Glioma