Clinical trial NCT06413706: A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioma
Keywords: Brain tumor
Central nervous system (CNS) tumor
Spinal cord tumor
Cyclin-dependent kinase (CDK) 4/6 inhibitor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-05-14
Enrollment: 45
Sex: ALL
Minimum age (years): 0
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Event Free Survival as Determined by Blinded Independent Review Committee
timeFrame: Baseline up to approximately 11 months
Secondary outcomes:
measure: Event Free Survival as Determined by Investigator Assessment
timeFrame: Baseline up to approximately 11 months
measure: Overall Survival (OS)
timeFrame: Baseline to date of death due to any cause (up to approximately 18 months)
measure: Overall Response Rate (ORR)
timeFrame: Baseline up to approximately 3 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline through to disease progression (up to approximately 3 months )
measure: Duration of Response (DoR)
timeFrame: 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 )
measure: Pharmacokinetic (PK): Abemaciclib Plasma Concentration
timeFrame: Cycle 1 through Cycle 4 (21 Day cycle)
measure: Abemaciclib Acceptability and Palatability Questionnaire
timeFrame: Day 1 of Cycles 1 through 3 (21 Day Cycles)]
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: Washington
country: United States
facility: Childrens National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health Systems
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester, Minnesota
state: Minnesota
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital/Hasbro Children's Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Children's Health
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Government - Lady Cilento Children's Hospital
state: Queensland
city: Nedlands
country: Australia
facility: Telethon Kids Institute-Perth Children's Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
state: Bruxelles-Capitale, Région De
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Liege
country: Belgium
facility: Centre Hospitalier Regional de la Citadelle
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital
state: Hovedstade
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
state: Bouches-du-Rhône
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux Groupe Hospitalier Pellegrin Hopital des Enfants
state: Gironde
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
state: Loire
city: Lille
country: France
facility: Centre Oscar Lambret
state: Nord-Pas-de-Calais
city: Villejuif
country: France
facility: Institut Gustave Roussy (Igr)
state: Paris
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-Alpes
city: Paris
country: France
facility: Institut Curie
city: Vandoeuvre-les-Nancy
country: France
facility: CHU de Nancy-Hopital de Brabois
city: Naples
country: Italy
facility: Azienda Ospedaliera Di Rilievo Nazionale Santobono Pausilipon
state: Campania
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
state: Liguria
city: Rome
country: Italy
facility: Ospedale Pediatrico Bambino Gesù
state: Roma
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
state: Veneto
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: Universita degli Studi di Torino
city: Nagoya
country: Japan
facility: Nagoya University Graduate School Of Medicine (Nugsm)
state: Aichi-Ken
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Utrecht
country: Netherlands
facility: Princess Maxima Center for Voor Kinderoncologie B.V
city: Bucharest
country: Romania
facility: Institutul Oncologic
state: București
city: Cluj
country: Romania
facility: Institutul Oncologic
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Hospital Sant Joan de Déu Barcelona
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid, Comunidad De
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
state: Madrid, Comunidad De
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia, Región De
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocio
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Eli Lilly and Company
name: Contact Lilly at 1-800-LillyRx (1-800-545-5979)
role: STUDY_DIRECTOR
References: