A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy
- Registration Number
- NCT06413706
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
- 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:
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Non-pontine diffuse midline glioma, H3 K27-altered,
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Diffuse hemispheric glioma, H3 G34-mutant
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Diffuse pediatric HGG, H3/IDH-wildtype
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Infant-type hemispheric glioma
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High-grade astrocytoma with piloid features
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High-grade pleomorphic xanthoastrocytoma
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IDH-mutant diffuse glioma with homozygous cyclin- dependent kinase inhibitor 2A/B (CDKN2A/B) deletion,
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IDH-mutant and 1p/19q co-deleted oligodendroglioma
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IDH-mutant astrocytoma with homozygous CDKN2A/B deletion
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Contraceptive use should be consistent with local regulations for participants in clinical studies.
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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.
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Minimum of 4 weeks between completion of radiation and Cycle 1 Day 1 (C1D1).
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Maximum of 8 weeks between completion of radiation and C1D1. Exceptional circumstances can be discussed with the medical monitor.
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Acute effects of prior therapies must be Grade ≤1 unless deemed clinically insignificant by the investigator.
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Adequate hematologic and organ function ≤7 days prior to C1D1
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Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment.
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A performance score of ≥60 using:
- Lansky scale for participants <16 years
- Karnofsky scale for participants ≥16 years
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Able to swallow and/or have a gastric/nasogastric tube.
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Any current systemic steroid use dose must be stable or decreasing at least 7 days prior to C1D1.
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Able and willing to adhere to study procedures, including frequent blood draws and MRI.
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At least 28 days since any major surgery, laparoscopic procedure, or a significant traumatic injury.
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Has a body surface area (BSA) of ≥0.2 m2.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abemaciclib + Temozolomide - Arm A Abemaciclib Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV). Abemaciclib + Temozolomide - Arm A Temozolomide Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV). Temozolomide - Arm B Temozolomide Participants will receive temozolomide administered orally or IV.
- Primary Outcome Measures
Name Time Method Event Free Survival as Determined by Blinded Independent Review Committee Baseline up to approximately 11 months Event free survival as determined by blinded independent review committee.
- Secondary Outcome Measures
Name Time Method Event Free Survival as Determined by Investigator Assessment Baseline up to approximately 11 months Event free survival as determined by investigator assessment
Overall Survival (OS) Baseline to date of death due to any cause (up to approximately 18 months) Overall survival
Overall Response Rate (ORR) Baseline up to approximately 3 months Overall response rate
Disease Control Rate (DCR) Baseline through to disease progression (up to approximately 3 months ) Disease control rate
Duration of Response (DoR) 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 ) Duration of response
Pharmacokinetic (PK): Abemaciclib Plasma Concentration Cycle 1 through Cycle 4 (21 Day cycle) PK Abemaciclib Plasma Concentrations
Abemaciclib Acceptability and Palatability Questionnaire Day 1 of Cycles 1 through 3 (21 Day Cycles)] 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.
Trial Locations
- Locations (47)
Centre Hospitalier Regional de la Citadelle
🇧🇪Liege, Belgium
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States
University of Michigan Health Systems
🇺🇸Ann Arbor, Michigan, United States
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Mays Cancer Center
🇺🇸San Antonio, Texas, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Queensland Government - Lady Cilento Children's Hospital
🇦🇺Brisbane, Queensland, Australia
Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin Hopital des Enfants
🇫🇷Bordeaux, Gironde, France
CHU de Nancy-Hopital de Brabois
🇫🇷Vandoeuvre-les-Nancy, France
Azienda Ospedaliera Di Rilievo Nazionale Santobono Pausilipon
🇮🇹Naples, Campania, Italy
Universita degli Studi di Torino
🇮🇹Torino, Italy
Nagoya University Graduate School Of Medicine (Nugsm)
🇯🇵Nagoya, Aichi-Ken, Japan
Princess Maxima Center for Voor Kinderoncologie B.V
🇳🇱Utrecht, Netherlands
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Clínico Universitario Virgen de la Arrixaca
🇪🇸El Palmar, Murcia, Región De, Spain
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
Nicklaus Children's Hospital
🇺🇸Miami, Florida, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Mayo Clinic in Rochester, Minnesota
🇺🇸Rochester, Minnesota, United States
Cincinnati Childrens Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Health
🇺🇸Dallas, Texas, United States
Cliniques universitaires Saint-Luc
🇧🇪Brussels, Bruxelles-Capitale, Région De, Belgium
UZ Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
Copenhagen University Hospital
🇩🇰Copenhagen, Hovedstade, Denmark
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
🇫🇷Marseille, Bouches-du-Rhône, France
Institut Gustave Roussy (Igr)
🇫🇷Villejuif, Paris, France
Centre Leon Berard
🇫🇷Lyon, Rhône-Alpes, France
Institut Curie
🇫🇷Paris, France
IRCCS Istituto Giannina Gaslini
🇮🇹Genova, Liguria, Italy
Ospedale Pediatrico Bambino Gesù
🇮🇹Rome, Roma, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Osaka City General Hospital
🇯🇵Osaka, Japan
National Center for Child Health and Development
🇯🇵Tokyo, Japan
Institutul Oncologic
🇷🇴Cluj, Romania
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital Sant Joan de Déu Barcelona
🇪🇸Esplugues de Llobregat, Barcelona, Spain
Hospital Infantil Universitario Niño Jesús
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Del Rocio
🇪🇸Sevilla, Spain
Hospital Universitari i Politecnic La Fe
🇪🇸València, Spain