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GlioblastomaEarly Phase 1NCT04391595

LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients

A Early Phase 1 study testing Abemaciclib and LY3214996 in people with Glioblastoma and GBM, run by Nader Sanai at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This trial is an open-label, multicenter, Phase 0/2 trial that will enroll up to 50 participants with recurrent glioblastoma which are schedule for resection. In the lead-in cohort, a total of 10 participants will be enrolled into the proposed phase 0 clinical trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma, GBM, Glioma
What is being tested?
Abemaciclib and LY3214996
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
3 sitesUnited States
Study dates
11 Jul 2020to 3 Sep 2025
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Prior resection of histologically diagnosed WHO Grade IV glioma defined as glioma participants 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.
  • Participants 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.
  • Sufficient archival tissue available to confirm eligibility.
  • For gliomas, archival tissue must demonstrate: (a) RB positivity (≥20%) on immunohistochemistry (IHC); or, no RB mutations on next-generation sequencing (NGS), (b) Chromosomal loss of CDKN2A/B/C; or, CDK4/6 amplification on array CGH or NGS, (c) pERK positivity (>30%) on IHC.
  • Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
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  • Participant 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.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
  • Age ≥18 at time of consent
  • Have a performance status (PS) ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982)
  • Ability to swallow oral medications.
  • Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
  • Adequate bone marrow function:
  • absolute neutrophil count ≥1,000/mcL
  • platelets (at time of surgery) ≥100,000/mcL
  • hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
  • Adequate hepatic function:
  • total bilirubin ≤1.5 X ULN Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
  • AST(SGOT) ≤3 X institutional ULN
  • ALT(SGPT) ≤3 X institutional ULN
  • Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.
  • For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 months after the end of treatment administration.
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 6 months after the end of treatment administration.
  • Agreement to adhere to Lifestyle Considerations throughout study duration
  • Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between last chemotherapy dose and Day 1 (provided the patient did not receive radiotherapy).
  • Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and Day 1.

Who cannot join

  • Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
  • Pregnancy or lactation.
  • Known allergic reactions to components of the abemaciclib or LY3214996.
  • Active infection or fever >38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.
  • Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis.
  • Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.
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  • Have history of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
  • Participant has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
  • Prior therapy with any CDK4/6 inhibitor or any ERK1/2 inhibitor. Prior therapy is defined as a therapeutic dosing.
  • Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
  • Have a mean QT interval corrected for heart rate (QTc) of ≥470 milliseconds on screening electrocardiogram (ECG) as calculated using the Bazett's formula.
  • The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Chandler Regional Medical Center

    Chandler, Arizona, 85224

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • HonorHealth Scottsdale Osborn Medical Center

    Scottsdale, Arizona, 85251

Other trials in United States

About this study

Official title: A Phase 0/2 Study of LY3214996 (ERK Inhibitor) in Combination With Abemaciclib (CDK4 and 6 Inhibitor) in Recurrent Glioblastoma Participants Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration

This trial is an open-label, multicenter, Phase 0/2 trial that will enroll up to 50 participants with recurrent glioblastoma which are schedule for resection. In the lead-in cohort, a total of 10 participants will be enrolled into the proposed phase 0 clinical trial. Participants will be administered LY3214996 plus Abemaciclib prior to surgical resection of their tumor. If positive PK results are demonstrated in ≥50% of Phase 0 participants and at least 5 participants are enrolled into Phase 2, up to approximately 40 additional participants will be enrolled in the dose expansion cohort in order to achieve a total of 25 participants enrolled into Phase 2 (lead-in cohort + dose expansion).

Conditions
Glioblastoma, GBM, Glioma
Being tested
Abemaciclib, LY3214996
Medical subject headings
Glioblastoma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AbemaciclibDrug

    100 mg of Abemaciclib BID for 11 doses over 5.5 days prior to surgical resection. Participants with tumors demonstrating PK-response in Phase 0 will continue treatment with recommended Phase 2 dose (RP2D) continuously in 21d cycles after surgery.

  • LY3214996Drug

    400 mg of LY3214996 daily for 6 doses over 5.5 days prior to surgical resection. Participants with tumors demonstrating PK-response in Phase 0 will continue treatment with recommended Phase 2 dose (RP2D) continuously in 21d cycles after surgery.

Study groups in NCT04391595
Study groupRoleWhat they receive
Arm 1Experimental400 mg of LY3214996 QD for 6 doses and 100 mg of Abemaciclib BID for 11 doses over 5.5 days prior to surgical resection. On Day 6, participants will receive Abemaciclib + LY3214996 dose 7 to 9 hours prior to craniotomy for tumor resection.
Receives: Drug: Abemaciclib; Drug: LY3214996

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 0: Pharmacokinetic analysis of tumor tissue

    Total and Unbound LY3214996 and Abemaciclib (and related M2 and M20 metabolites) concentration in enhancing and non-enhancing tumor tissue

    Measured: 8 hour

  2. Phase 0: Pharmacokinetic analysis of cerebrospinal fluid (CSF)

    Total and Unbound LY3214996 and Abemaciclib (and related M2 and M20 metabolites) concentration in CSF

    Measured: 8 hour

  3. Pharmacokinetic analysis of plasma

    Total and Unbound LY3214996 and Abemaciclib (and related M2 and M20 metabolites) concentration in plasma

    Measured: Day 6 at 0, 0.5, 1, 2, 4, 6, 8, 12 and 24 hours post dose

  4. Phase 2: Progression-free survival

    Phase 2: 6-month progression-free survival (PFS6) rate measured from time of surgery to date of recurrence

    Measured: up to 60 months

Secondary outcomes (6)

  1. Phase 0: PD Analysis

    Phase 0: percentage of pRSK+, pERK+, pRB+, pFOXM1, MIB-1+ and Cleaved Caspase 3+ cells from the surgical tissue will be quantified and compared to baseline archival tissue.

    Measured: Intraoperatively

  2. Number of Adverse Events

    Number of Adverse Events

    Measured: up to 30 days after the last study dose

  3. Incidence of drug-related toxicity

    Drug-related toxicity

    Measured: up to 30 days after the last study dose

  4. Incidence of treatment-emergent adverse events

    Treatment-emergent adverse events

    Measured: up to 30 days after the last study dose

  5. Deaths

    Deaths

    Measured: up to 60 months

  6. Incidence of clinical laboratory abnormalities per CTCAE

    Clinical laboratory abnormalities per CTCAE

    Measured: up to 30 days after the last study dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2020
  2. Study start11 Jul 2020
  3. Primary completion27 Jul 2023
  4. Study completion3 Sep 2025

Resources

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
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04391595
Sponsor's protocol ID
2019-07
Status last verified
Mar 2026
First submitted
12 May 2020
Last updated
6 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Abemaciclib and LY3214996 in people with Glioblastoma and GBM, run by Nader Sanai at 3 sites 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 26 inclusion and 12 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: finished, 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 3 sites 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Phase 0: Pharmacokinetic analysis of tumor tissue (time frame: 8 hour). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04391595.

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.

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