Glioblastoma MultiformeEarly Phase 1NCT02933736
Ribociclib (LEE011) in Preoperative Glioma and Meningioma Patients
A Early Phase 1 study testing Ribociclib in people with Glioblastoma Multiforme and Meningioma, run by Nader Sanai at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme, Meningioma
- What is being tested?
- Ribociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Oct 2016to Mar 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- INR ≤1.5
- Serum creatinine < 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
- In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN.
- Serum total bilirubin < ULN, or < 3.0 x ULN in patients with well-documented Gilbert's syndrome.
- Patient with available standard 12-lead ECG with the following parameters at screening (defined as the mean of the ECGs):
- QTcF interval at screening < 450 msec (using Fridericia's correction)
- Resting heartrate 50-90 bpm
- Must be able to swallow ribociclib capsules/tablets
- If patient is receiving tamoxifen or toremifene, a washout period of 5 half-lives prior to enrollment is required
Who cannot join
- 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
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- 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)
- Documented cardiomyopathy
- Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
- Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)
- Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
- Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
- Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)
- Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at screening
- Currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:
- Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pomelos/pummelos, star-fruit, pomegranates or pomegranate juice and Seville oranges
- That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
- Herbal preparations/medications, dietary supplements known as strong inhibitors or inducers of CYP3A4 or those with a known risk of QT prolongation. (Does not include Ca, Mg, Vit D or KCl supplements).
- Currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
- Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
- Major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
- Has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 Grade <1 (Exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the study.).
- Child-Pugh score B or C.
- History of non-compliance to medical regimen.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.]
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months after the last dose of study treatment. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- Male sterilization (at least 6 months prior to screening) with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate. For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
- Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
- In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
- Note: Oral contraceptives are allowed but should be used in conjunction with a barrier method of contraception due to unknown effect of drug-drug interaction.
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- Sexually active males unless they use a condom during intercourse while taking drug and for 21 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Ribociclib
- Medical subject headings
- Glioblastoma, Meningioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibociclibDrug
Also called LEE011
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Exposure
Measured: 0.5, 1, 2, 4, 6, 8, and 24 hours post-last 900 mg dosing
CSF Penetration
Measured: 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.
Measured: Days 1, 22, 43, 64 (add 21 day intervals)...until disease returns or side effect preventing participation in study occurs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2016 (estimated)
- Study start17 Oct 2016
- Primary completion1 Mar 2023
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nader Sanai
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, Ivy Brain Tumor Center, Barrow Neurological Institute
- Responsible party
- Sponsor-investigator, Nader Sanai, St. Joseph's Hospital and Medical Center, Phoenix
- Investigators
- Nader Sanai, MD, Principal investigator, Deputy Director of the Ivy Brain Tumor Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02933736
- Sponsor's protocol ID
- PHX-16-0116-80-12
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2016
- Last updated
- 6 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02933736
- Acronym / sponsor ID
- PHX-16-0116-80-12
- Conditions
- Glioblastoma Multiforme, Meningioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Nader SanaiUniversity, hospital or other
- Collaborators
- Novartis, Ivy Brain Tumor Center, Barrow Neurological Institute
- Study start
- 17 Oct 2016 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- Mar 2027 (estimated)
- First posted
- 14 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Administration of ribociclib | Experimental | Drug: RibociclibSubjects 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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
Key exclusion criteria (43 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RibociclibAlso: LEE011 | Drug | Administration of ribociclib |
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nader Sanai, MD principal investigator
Deputy Director of the Ivy Brain Tumor Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ribociclib in people with Glioblastoma Multiforme and Meningioma, run by Nader Sanai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Exposure (time frame: 0.5, 1, 2, 4, 6, 8, and 24 hours post-last 900 mg dosing). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026.