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.
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.
∙ 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.
• Cardiac Function: Normal ejection fraction (ECHO or cardiac MRI) \>= 53% (or the institutional normal); QTC or 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 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 include intrauterine devices (IUD), hormonal (birth control pills, injections, implants), tubal ligation, or partner s 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)