Clinical Trial: Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Nervo

Brief 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 Summary:

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..
Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Current Primary Outcome:

  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: St. Joseph's Hospital and Medical Center, Phoenix

Dates:
Date Received: October 12, 2016
Date Started: October 2016
Date Completion: April 2019
Last Updated: January 4, 2017
Last Verified: January 2017