A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy

A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib in Combination With Temozolomide Compared to Temozolomide Monotherapy in Children and Young Adults With Newly Diagnosed High-Grade Glioma Following Radiotherapy

The purpose of this study is to measure the benefit of adding abemaciclib to the chemotherapy, temozolomide, for newly diagnosed high-grade glioma following radiotherapy.

Your participation could last approximately 11 months and possibly longer depending upon how you and your tumor respond.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioma
• Intervention / Treatment: Drug: Abemaciclib; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4101
    • Queensland Government- Lady Cilento Children's Hospital
  • Nedlands, Australia, 6009
    • Perth Children's Hospital
  • Westmead, Australia, 2145
    • The Children's Hospital at Westmead
• Belgium
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent (Uz Gent)
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven
  • Woluwe-Saint-Lambert, Belgium, 1200
    • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen University Hospital-Rigshospitalet University Hospital
• France
  • Bordeaux, France, 33076
    • Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin Hopital des Enfants
  • Lille, France, 59020
    • Centre de Lutte Contre le Cancer (CLCC) - Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Leon Berard
  • Marseille, France, 13885
    • Hopital La Timone
  • Paris, France, 75005
    • Institut Curie
  • Villejuif, France, 94805
    • Institut Gustave Roussy-Gustave Roussy Cancer Center -Ditep
• Italy
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Naples, Italy, 80129
    • Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
  • Rome, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Universita Cattolica del Sacro Cuore
• Japan
  • Nagoya, Japan, 466-8560
    • Nagoya University Hospital
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Setagaya-Ku Tokyo, Japan, 157-8535
    • National Center for Child Health and Development (NCCHD)
• Netherlands
  • Utrecht, Netherlands, 3584 CS
    • Princess Maxima Center for Voor Kinderoncologie B.V
• Romania
  • Cluj-Napoca, Romania, 400015
    • Institutul Oncologic Prof. Dr. Ion Chiricuta
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Esplugues de Llobregat, Spain, 08950
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Nino Jesus (HIUNJS)
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46026
    • Universitat de Valencia - Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County - Orange
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital (LPCH) - Stanford University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital (JHH) - Johns Hopkins Childrens Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System (UMHS) - C.S. Mott Children's Hospital - Hematology Oncology Clinic
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern Medical Center Dallas/Childrens Medical Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biopsy proven high-grade glioma (HGG) as defined by 2016 World Health Organization (WHO) Classification Criteria, Grade 3-4 including:
• Anaplastic astrocytoma
• Anaplastic ganglioglioma
• Anaplastic oligodendroglioma.
• Anaplastic pleomorphic xanthoastrocytoma,
• Glioblastoma

OR as defined by the 2021 WHO Classification Criteria as molecularly characterized:

• Non-pontine diffuse midline glioma, H3 K27-altered,
• Diffuse hemispheric glioma, H3 G34-mutant
• Diffuse pediatric HGG, H3/IDH-wildtype
• Infant-type hemispheric glioma
• High-grade astrocytoma with piloid features
• High-grade pleomorphic xanthoastrocytoma
• IDH-mutant diffuse glioma with homozygous cyclin- dependent kinase inhibitor 2A/B (CDKN2A/B) deletion,
• IDH-mutant and 1p/19q co-deleted oligodendroglioma
• IDH-mutant astrocytoma with homozygous CDKN2A/B deletion
• Contraceptive use should be consistent with local regulations for participants in clinical studies.
• Radiotherapy initiated within 6 weeks (+1 week) of diagnosis and administered over 6 weeks (±1 week). Participants <3 years of age, considered not suitable for radiotherapy may be eligible.
• Minimum of 4 weeks between completion of radiation and Cycle 1 Day 1 (C1D1).
• Maximum of 8 weeks between completion of radiation and C1D1. Exceptional circumstances can be discussed with the medical monitor.
• Acute effects of prior therapies must be Grade ≤1 unless deemed clinically insignificant by the investigator.
• Adequate hematologic and organ function ≤7 days prior to C1D1
• Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment.

• A performance score of ≥60 using:

  1. Lansky scale for participants <16 years
  2. Karnofsky scale for participants ≥16 years
• Able to swallow and/or have a gastric/nasogastric tube.
• Any current systemic steroid use dose must be stable or decreasing at least 7 days prior to C1D1.
• Able and willing to adhere to study procedures, including frequent blood draws and MRI.
• At least 28 days since any major surgery, laparoscopic procedure, or a significant traumatic injury.
• Has a body surface area (BSA) of ≥0.2 m2.

Exclusion Criteria:

Participants are excluded if any of the following apply:

• Diffuse Intrinsic Pontine Glioma (DIPG) or diffuse midline glioma located in the pons.
• Recurrent or refractory HGG including any recurrence/progression during/after radiotherapy.
• Secondary HGG, defined as a previously treated low-grade glioma that now meets high- grade criteria, or that resulted from a previously treated malignancy.
• Have known pathogenic somatic mutations appropriate for an anaplastic lymphoma kinase (ALK), B-rapidly accelerated fibrosarcoma (BRAF), or neurotrophic tyrosine receptor kinase (NTRK ) inhibitor, in regions where these therapies are available and deemed appropriate by the investigator.
• Prior HGG treatment (including bevacizumab), except for surgery and radiotherapy (with or without concomitant temozolomide).
• Current enrollment in another trial deemed incompatible with this study.
• Treatment with an investigational product within the last 30 days or 5 half-lives (whichever is longer).
• Prior malignancy within the previous 3 years that, per the investigator and the medical monitor, may affect interpretation of study results.
• A preexisting medical condition(s) that, per the investigator, would preclude study participation.
• Any serious, active, systemic infection requiring IV antibiotic, antifungal, or antiviral therapy, including acute hepatitis B or C, or Human Immunodeficiency Virus at C1D1.
• Intolerability or hypersensitivity such as urticaria, anaphylaxis, toxic necrolysis, and/or Stevens-Johnson syndrome to temozolomide, and/or abemaciclib, their excipients, or dacarbazine.
• Received a live virus vaccine within 28 days of C1D1.
• Pregnant, breastfeeding, or intend to become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abemaciclib + Temozolomide - Arm A; Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV).	Drug: Abemaciclib; Administered orally; Other Names: LY2835219; Drug: Temozolomide; Administered orally or IV
Active Comparator: Temozolomide - Arm B; Participants will receive temozolomide administered orally or IV.	Drug: Temozolomide; Administered orally or IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival as Determined by Blinded Independent Review Committee	Event free survival as determined by blinded independent review committee.	Baseline up to approximately 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival as Determined by Investigator Assessment	Event free survival as determined by investigator assessment	Baseline up to approximately 11 months
Overall Survival (OS)	Overall survival	Baseline to date of death due to any cause (up to approximately 18 months)
Overall Response Rate (ORR)	Overall response rate	Baseline up to approximately 3 months
Disease Control Rate (DCR)	Disease control rate	Baseline through to disease progression (up to approximately 3 months )
Duration of Response (DoR)	Duration of response	Date of Complete Response (CR) or Partial Response (PR) or Minor Response (MR) to date of disease progression or death (up to approximately 3 months )
Pharmacokinetic (PK): Abemaciclib Plasma Concentration	PK Abemaciclib Plasma Concentrations	Cycle 1 through Cycle 4 (21 Day cycle)
Abemaciclib Acceptability and Palatability Questionnaire	Participants evaluated abemaciclib acceptability (palatability and ease of administration) using a 5-category questionnaire. Participants were asked to select one of the following to describe the acceptability of abemaciclib: Very difficult, difficult, neither easy nor difficult, easy, or very easy.	Day 1 of Cycles 1 through 3 (21 Day Cycles)]

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: May 9, 2024
• First Submitted That Met QC Criteria: May 9, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Brain tumor; Central nervous system (CNS) tumor; Spinal cord tumor; Cyclin-dependent kinase (CDK) 4/6 inhibitor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Central Nervous System Neoplasms; Spinal Cord Diseases; Neoplasms; Glioma; Brain Neoplasms; Spinal Cord Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Dacarbazine; Triazenes; Imidazoles; Temozolomide; abemaciclib
• Other Study ID Numbers: 18646; I3Y-MC-JPEH (Other Identifier: Eli Lilly and Company); 2022-502269-13-00 (Ctis); U1111-1289-0405 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No