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: Not yet recruiting
• Conditions: Glioma
• Intervention / Treatment: Drug: Abemaciclib; Drug: Temozolomide

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

Contacts and Locations

• Study Contact: Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 317-615-4559; Email: ClinicalTrials.gov@lilly.com
• Study Contact Backup: Name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 : Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 97557
      • Phoenix Childrens Hospital (PCH)
      • Principal Investigator: Lindsey M Hoffman

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
• 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.

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	Questionnaire	Day 1 of Cycles 1 through 3 (21 Day Cycles)]

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Contact Lilly at 1-800-LillyRx (1-800-545-5979), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): July 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 14, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

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: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• 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