Menu
  • Find a Doctor
  • International Patients
  • Contact Us
  • Patients & Families
  • Education
  • Research
  • Departments & People
  • News & Stories
  • Transfer a Patient
  • Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients

    In the proposed trial, patients will be administered ribociclib prior to surgical resection of their tumor. Patients will be enrolled in time-intervals sequentially (non-randomized). All patients will be orally-administered 5 doses of LEE011 (900 mg/d) with the final dose occurring at one of 3 intervals before brain tumor resection.

    900 mg/d is the maximally tolerated dose (MTD), as determined in a recent Novartis-sponsored Phase I study for advanced solid tumor patients. The recommended dose expansion and Phase 2 is 600mg/d for 3 weeks on and 1 week off. Due to drug pharmacokinetics, the MTD (900mg) dose will be used for pre-surgical dosing in order to maximize the opportunity to identify relevant tumor pharmacokinetic and pharmacodynamics endpoints.

    To assess the PK, PD, and PG endpoints listed above, CSF and brain tumor tissue will be collected intraoperatively (for gliomas, enhancing and non-enhancing tumor tissue will be collected and analyzed separately). Additionally, blood samples will be obtained at 0.5, 1, 2, 4, 6, 8, and 24 hours after the final ribociclib dose is administered.

    Patients with tumors demonstrating positive PK, PD, and PG effects will continue treatment with ribociclib (21 days on, 7 days off) after surgery. This will constitute the Phase II component of the study. Patients will be treated until unacceptable toxicity is observed, or until disease progression as assessed by radiographic or clinical metrics. Preliminary rates of progression-free survival in patients with high-grade gliomas and high-grade meningiomas treated with ribociclib will be measured through radiographic and clinical response metrics, specifically Response Assessment in Neuro-Oncology (RANO) criteria and investigator discretion. Overall survival in patients with high-grade gliomas and high-grade meningiomas treated with ribociclib will be assessed by medical record review and survival follow up. Common Toxicity Criteria Adverse Event (CTC AE 4.0) will be utilized to review ribociclib treatment effects in patients with brain tumors. The trough plasma samples of ribociclib will be collected at pre-dosing on each clinical visit day (e.g., days 1, 22, 43, 64…) prior to the administration of ceritinib on that day. Ribociclib will be administered in the clinics on the clinic visit days to ensure the collection of trough level samples.

    Ribociclib and Everolimus for Glioblastoma Multiforme

    In the proposed trial, patients will be administered ribociclib+everolimus prior to surgical resection of their tumor. Recurrent GBM patients will be randomized into one of the three time-interval cohorts.

    All patients will receive ribociclib 400 mg and everolimus 2.5 mg (R2P2D) orally-administered in 5 daily doses with the last dose being administered at one of 3 intervals before brain tumor resection:

    • Cohort 1: last ribociclib+everolimus dose 2 to 4 hours prior to craniotomy for tumor resection (n=8 patients)
    • Cohort 2: last ribociclib+everolimus dose 8 to 10 hours prior to craniotomy for tumor resection (n=8 patients)
    • Cohort 3: last ribociclib+everolimus dose 24 to 26 hours prior to craniotomy for tumor resection (n=8 patients) To assess the PK and PD endpoints listed above, blood, CSF and brain tumor tissue will be collected intraoperatively (enhancing and non-enhancing tumor tissue will be collected and analyzed separately). Additionally, blood samples will be obtained on Day 4 (the day before the surgery for Cohorts 1 & 2; 2 days before surgery for Cohort 3) at pre-dosing (trough level), 0.5, 1, 2, 4, 7 hours post dose. A pre-dosing (trough level) blood sample will also be obtained on Day 5.

    Patients with tumors demonstrating favorable PK and PD will continue treatment with RP2D continuously in 28d cycles after surgery. This will constitute the Phase II component of the study. Patients will be treated until unacceptable toxicity is observed, or until disease progression as assessed by radiographic or clinical metrics. Preliminary rates of progression-free survival in patients with high-grade gliomas treated with ribociclib+everolimus will be measured through radiographic and clinical response metrics, specifically Response Assessment in Neuro-Oncology (RANO) criteria and investigator discretion. Overall survival in patients with high-grade gliomas treated with ribociclib+everolimus will be assessed by medical record review and survival follow up. Common Toxicity Criteria Adverse Event (CTC AE 4.03) will be utilized to review ribociclib+everolimus treatment effects in patients with brain tumors.

    In Phase II portion, trough steady-state blood samples will be obtained on days 1, 8, 15, and 22 of each cycle prior to the administration of ribociclib+everolimus on that day. Note: ribociclib+everolimus will be administered in the clinics on the clinic visit days to ensure the collection of trough level samples.

    About Barrow Neurological Institute

    Since our doors opened as a regional specialty center in 1962, we have grown into one of the premier destinations in the world for neurology and neurosurgery. Our experienced, highly skilled, and comprehensive team of neurological specialists can provide you with a complete spectrum of care–from diagnosis through outpatient neurorehabilitation–under one roof. Barrow Neurological Institute: Discover. Educate. Heal.