NCT02933736

Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients

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

• Status: Active Not Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Nader Sanai · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 (PK) and pharmacodynamics (PD) endpoints. To assess the PK, and PD endpoints listed above, cerebrospinal fluid (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 and PD 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.

Conditions

• Glioblastoma Multiforme
• Meningioma

Interventions

Type	Name	Description
DRUG	Ribociclib

Timeline

• Start date: 2016-10-17
• Primary completion: 2023-03-01
• Completion: 2027-03-01
• First posted: 2016-10-14
• Last updated: 2026-03-06

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study