Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients
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|ClinicalTrials.gov Identifier: NCT02933736|
Recruitment Status : Recruiting
First Posted : October 14, 2016
Last Update Posted : January 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme Meningioma||Drug: Ribociclib||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 0/II Study of Ribociclib (LEE011) in Preoperative Rb-Positive Recurrent High-Grade Glioma and Meningioma Patients Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||April 2019|
Experimental: Administration of ribociclib
Subjects will be administered ribociclib prior to surgical resection of their tumor. Ribociclib administration will occur at sequential time-intervals (i.e.,Cohort 1 will be filled first with 16 subjects, then Cohort 2 the same, followed by Cohort 3). All patients will be orally-administered 5 doses of LEE011 (900 mg/d) with the final dose occurring at one of 3 following intervals before brain tumor resection:
Cohort 1: last ribociclib dose 2-4 hours prior to craniotomy for tumor resection
Cohort 2: last ribociclib dose 4-8 hours prior to craniotomy for tumor resection
Cohort 3: last ribociclib dose 22-26 hours prior to craniotomy for tumor resection
Other Name: LEE011
- Plasma Exposure [ Time Frame: 0.5, 1, 2, 4, 6, 8, and 24 hours post-last 900 mg dosing ]
- CSF Penetration [ Time Frame: 2-4, 6-8, and 23-25 hours post-last 900 mg dosing ]
- Brain Accumulation of Ribociclib [ Time Frame: Days 1, 22, 43, 64 (add 21 day intervals)...until disease returns or side effect preventing participation in study occurs ]This is the Phase II portion, which assesses trough plasma concentrations of study drug on each clinical visit day, prior to administration of ribociclib on that day.
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): NCT02933736
|Contact: Norissa Honea, RN, PhDfirstname.lastname@example.org|
|United States, Arizona|
|Barrow Brain and Spine||Recruiting|
|Phoenix, Arizona, United States, 85013|
|Contact: Norissa Honea, RN, PhD 602-406-6267 email@example.com|
|Principal Investigator: Nader Sanai, MD|
|Principal Investigator:||Nader Sanai, MD||Barrow Brain and Spine|