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

Glioma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06413706
• Other study ID #: 18646
• Secondary ID: I3Y-MC-JPEH2022-
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: February 2028

Study information

• Verified date: June 2024
• Source: Eli Lilly and Company
• Contact: There may be multiple sites in this clinical trial. 1-877-CTLILL
• Phone: 317-615-4559
• Email: ClinicalTrials.gov[@]lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 45
• Est. completion date: February 2028
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 20 Years

Eligibility

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

• Isocitrate dehydrogenase-mutant (IDH-mutant) 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 foe 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.

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, its excipients, or dacarbazine.

• Received a live virus vaccine within 28 days of C1D1.

• Pregnant, breastfeeding, or intend to become pregnant during the study.

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• Abemaciclib
Administered orally
• Temozolomide
Administered orally or IV

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels	Bruxelles-Capitale
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Denmark	Rigshospitalet	Copenhagen	Hovedstaden
France	Centre Leon Berard	Lyon	Rhône-Alpes
France	Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone	Marseille	Bouches-du-Rhône
France	Institut Curie	Paris
France	Gustave Roussy	Villejuif	Val-de-Marne
Italy	IRCCS Istituto Giannina Gaslini	Genova	Liguria
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan	Lombardia
Italy	Azienda Ospedaliera di Rilievo Nazional Santobono Pausilipon	Napoli	Campania
Italy	Ospedale Pediatrico Bambino Gesù	Rome	Roma
Japan	Osaka City General Hospital	Osaka
Japan	National Center for Child Health and Development	Tokyo
Romania	Institutul Oncologic	Bucharest	Bucure?ti
Romania	Institutul Oncologic	Cluj
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Hospital Sant Joan de Déu	Esplugues de Llobregat	Barcelona [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
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	Children's Health	Dallas	Texas
United States	Spectrum Health	Grand Rapids	Michigan
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Children's Hospital of Orange County	Orange	California
United States	Lucile Packard Children's Hospital	Palo Alto	California
United States	Phoenix Childrens Hospital (PCH)	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  France,  Italy,  Japan,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Event Free Survival as Determined by Investigator Assessment	Event free survival as determined by investigator assessment	Baseline up to approximately 11 months
Secondary	Overall Survival (OS)	Overall survival	Baseline to date of death due to any cause (up to approximately 18 months)
Secondary	Overall Response Rate (ORR)	Overall response rate	Baseline up to approximately 3 months
Secondary	Disease Control Rate (DCR)	Disease control rate	Baseline through to disease progression (up to approximately 3 months )
Secondary	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 )
Secondary	Pharmacokinetic (PK): Abemaciclib Plasma Concentration	PK Abemaciclib Plasma Concentrations	Cycle 1 through Cycle 4 (21 Day cycle)
Secondary	Abemaciclib Acceptability and Palatability Questionnaire	Questionnaire	Day 1 of Cycles 1 through 3 (21 Day Cycles)]