Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients

NCT02933736 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: PHX-16-0116-80-12
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Meningioma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (3)

• Plasma Exposure

  0.5, 1, 2, 4, 6, 8, and 24 hours post-last 900 mg dosing

• CSF Penetration

  2-4, 6-8, and 23-25 hours post-last 900 mg dosing

• Brain Accumulation of Ribociclib

  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.

  Days 1, 22, 43, 64 (add 21 day intervals)...until disease returns or side effect preventing participation in study occurs

Study Arms (1)

Administration of ribociclib

EXPERIMENTAL

Subjects will be administered ribociclib prior to surgical resection of their tumor. 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 6-8 hours prior to craniotomy for tumor resection Cohort 3: last ribociclib dose 23-25 hours prior to craniotomy for tumor resection

Drug: Ribociclib

Interventions

Ribociclib DRUG

Also known as: LEE011

Administration of ribociclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One prior resection of histologically-diagnosed World Health Organization (WHO) Grade III or IV glioma, or WHO grade II or III meningioma.
• MRI evidence of disease recurrence
• For gliomas, archival tissue must demonstrate: (a) RB positivity on immunohistochemistry OR no RB mutations on next-gen sequencing (NGS), (b) Chromosome 9p21.3 deletion on FISH OR CDKN2A/B/C loss on array CGH OR CDK4/6 or CCND1/2 amplification on array CGH.
• For meningiomas, archival tissue much demonstrate (a) RB positivity on immunohistochemistry OR no RB mutations on next-gen sequencing (NGS).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Patients ≥ 18 years of age
• Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
• Patient has voluntarily agreed to participate by giving written informed consent (personally or via legally-authorized representative(s), and assent if applicable).
• (Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.)
• Patients must have recovered from all toxicities related to prior anticancer therapies to ≤ grade 2 (CTCAE v 4.03), provided that concomitant medication is given prior to initiation of treatment with ribociclib. Exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment.
• The following laboratory criteria have been met:
• Absolute neutrophil count (ANC) ≥1.5 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥100 x 10\^9/L
• Potassium, total calcium (corrected for serum albumin), magnesium, and sodium within normal limits for the institution or corrected to within normal limits with supplements before first dose of study medication.

You may not qualify if:

• Archival tissue not available for research use.
• Archival tumor not Rb-positive status
• No prior radiotherapy
• Co-morbid condition(s) that, at the opinion of the investigator, prevent safe surgical treatment
• Active infection or fever \> 38.5°C
• Patients with known hypersensitivity to any of the excipients of ribociclib
• Patients with known hypersensitivity to peanut, soy or lactose
• Prior therapy with ribociclib.
• Patient has a concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• History of HIV infection (testing not mandatory).
• Other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol.
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities.
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)

Sponsors & Collaborators

• Nader Sanai: lead
• Novartis: collaborator
• Ivy Brain Tumor Center: collaborator
• Barrow Neurological Institute: collaborator

Study Sites (1)

Barrow Brain and Spine

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Glioblastoma; Meningioma

Interventions

ribociclib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Study Officials

• Nader Sanai, MD

  Deputy Director of the Ivy Brain Tumor Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Ivy Brain Tumor Center

Study Record Dates

• First Submitted: October 12, 2016
• First Posted: October 14, 2016
• Study Start: October 17, 2016
• Primary Completion: March 1, 2023
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)