Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
Searching Both is inclusive of interventional and observational studies.
|Eligible Ages||18 Years - 39 Years|
INCLUSION 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.
- - Participants who have received prior treatment with abemaciclib or another specific CDK4/6 inhibitor are not eligible for enrollment (ex.
- - 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 randomization.
- - Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy.
- - 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.
- - 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.
- - 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.
- - 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].
- - Requires treatment with strong/moderate CYP3A inhibitors or inducers.
- - Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol (see Study Procedure Manual).
- - 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.
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|National Cancer Institute (NCI)|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Sadhana Jackson, M.D.|
|Principal Investigator Affiliation||National Cancer Institute (NCI)|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Study Website:||View Trial Website|
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 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. CDKN2A is the primary inhibitory brake on CDK4/6 driven signaling and is commonly deleted in glioblastoma, pancreas, bladder, breast and prostate cancer. The specific CDK4/6 inhibitor, abemaciclib, has 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 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.#46; 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 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 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 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 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 CDK inhibition (decreased expression of Rb and/or 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 BID together with temozolomide 200mg/m2 po daily x 5 days in 28 day cycles (temozolomide 150mg/m2 po daily x 5 days for cycle 1). After every 3 cycles, repeat brain MRI s 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 7 participants.
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)
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.