A Phase 0 /II Study of Ribociclib (LEE011) in Combination With Everolimus in Preoperative Recurrent High-Grade Glioma Patients Scheduled for Resection

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen byNader Sanai, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

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

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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 for the first two dose levels. In the lead-in dose escalation study, the first six subjects (lead-in) will receive ribociclib 400 mg and everolimus 2.5 mg orally-administered in 5 daily doses with the last dose. If one or less patient experiences DLT among the 6 patients, this regimen with ribociclib 400 mg and everolimus 2.5mg will be considered safe and we will continue with the dose escalation phase of the study up to Level 3. Four dose escalation levels: Level 0: ribociclib 400mg and everolimus 2.5 Level 1: ribociclib 600mg and everolimus 2.5mg Level 2: ribociclib 600mg and everolimus 5mg Level 3: ribociclib 600mg and everolimus 10mg

Research Team

Nader Sanai, MD

Principal Investigator

Deputy Director of the Ivy Brain Tumor Center

Eligibility Criteria

Inclusion Criteria

Prior resection of histologically-diagnosed WHO Grade III or IV glioma. A. Glioma patients who have progressed on or following standard (Stupp regimen) therapy, which included maximal surgical resection, temozolomide, and fractionated radiotherapy.

Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI.

Subjects must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.

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Treatment Details

Interventions

Everolimus (mTOR Inhibitor)
Ribociclib (CDK4/6 Inhibitor)

Participant Groups

3Treatment groups

Experimental Treatment

Group I: Cohort 3: last dose 23 to 25 hours prior to resectionExperimental Treatment2 Interventions

Three to fourteen patients will receive ribociclib and everolimus orally-administered in 5 daily doses with the last dose being administered at one of 3 intervals before brain tumor resection: • Cohort 3: last ribociclib+everolimus dose 23 to 25 hours prior to craniotomy for tumor resection

Group II: Cohort 2: last dose 7 to 9 hours prior to resectionExperimental Treatment2 Interventions

Three to fourteen patients will receive ribociclib and everolimus orally-administered in 5 daily doses with the last dose being administered at one of 3 intervals before brain tumor resection: • Cohort 2: last ribociclib+everolimus dose 7 to 9 hours prior to craniotomy for tumor resection

Group III: Cohort 1: last dose 1 to 3 hours prior to resectionExperimental Treatment2 Interventions

Three to fourteen patients will receive ribociclib and everolimus 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 1 to 3 hours prior to craniotomy for tumor resection