A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy for Pediatric High-grade Glioma

JRCT ID: jRCT2051240121

Registered date:05/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: High-Grade Glioma
• Date of first enrollment: 10/09/2024
• Target sample size: 6
• Countries of recruitment: Australia,Japan,Belgium,Japan,France,Japan,Italy,Japan,Netherlands,Japan,Spain,Japan,the US,Japan,Denmark,Japan,Romania,Japan
• Study type: Interventional

Intervention(s)

Drug: Abemaciclib
Administered orally
Other Names: LY2835219
Drug: Temozolomide
Administered orally or IV (If approved by medical monitor)

Arm A: Abemaciclib + Temozolomide
Arm B: Temozolomide

Outcome(s)

• Primary Outcome: Event Free Survival as determined by Blinded Independent Review Committee

Secondary Outcome

-Event Free Survival as determined by investigator assessment
-Overall Survival
-Overall Response Rate
-Disease Control Rate
-Duration of Response
-Safety
-Abemaciclib Plasma Concentrations
-Participant and/or caregiver reported acceptability and palatability

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: < 21age old

Include criteria

Subjects required to meet all the folloiwng 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
-Patients who consent to use effective methods of contraception which meets the study criteria.
-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 date of initial treatment (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:
a) Lansky scale for participants <16 years
b) 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.
-Capable of giving sign on informed consent form or assent.

Exclude criteria

Patients who meets any of the following criteria cannot participate in this clinical trial.
-Diffuse Intrinsic Pontine Glioma (DIPG) or diffuse midline glioma located in the ?
-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.
-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 Information

• Primary Sponsor: Masaki Takeshi
• Secondary ID(s): NCT06413706