## Protocol Section
### Identification Module
**NCT ID:** NCT06413706

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 18646
#### Organization
**Class:** INDUSTRY
**Full Name:** Eli Lilly and Company
#### Secondary ID Infos
**Domain:** Eli Lilly and Company
**ID:** I3Y-MC-JPEH
**Type:** OTHER
**ID:** 2022-502269-13-00
**Type:** CTIS
**Domain:** UTN
**ID:** U1111-1289-0405
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2028-02

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-14

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-09

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-14
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-09
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Eli Lilly and Company

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Glioma

**Keywords:**

- Brain tumor

- Central nervous system (CNS) tumor

- Spinal cord tumor

- Cyclin-dependent kinase (CDK) 4/6 inhibitor

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 45

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV).

**Intervention Names:**

- Drug: Abemaciclib

- Drug: Temozolomide

**Label:** Abemaciclib + Temozolomide - Arm A

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive temozolomide administered orally or IV.

**Intervention Names:**

- Drug: Temozolomide

**Label:** Temozolomide - Arm B

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Abemaciclib + Temozolomide - Arm A

**Description:** Administered orally

**Name:** Abemaciclib

**Other Names:**

- LY2835219

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Abemaciclib + Temozolomide - Arm A

- Temozolomide - Arm B

**Description:** Administered orally or IV

**Name:** Temozolomide

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Event free survival as determined by blinded independent review committee.

**Measure:** Event Free Survival as Determined by Blinded Independent Review Committee

**Time Frame:** Baseline up to approximately 11 months

#### Secondary Outcomes

**Description:** Event free survival as determined by investigator assessment

**Measure:** Event Free Survival as Determined by Investigator Assessment

**Time Frame:** Baseline up to approximately 11 months

**Description:** Overall survival

**Measure:** Overall Survival (OS)

**Time Frame:** Baseline to date of death due to any cause (up to approximately 18 months)

**Description:** Overall response rate

**Measure:** Overall Response Rate (ORR)

**Time Frame:** Baseline up to approximately 3 months

**Description:** Disease control rate

**Measure:** Disease Control Rate (DCR)

**Time Frame:** Baseline through to disease progression (up to approximately 3 months )

**Description:** Duration of response

**Measure:** Duration of Response (DoR)

**Time Frame:** 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 )

**Description:** PK Abemaciclib Plasma Concentrations

**Measure:** Pharmacokinetic (PK): Abemaciclib Plasma Concentration

**Time Frame:** Cycle 1 through Cycle 4 (21 Day cycle)

**Description:** Questionnaire

**Measure:** Abemaciclib Acceptability and Palatability Questionnaire

**Time Frame:** Day 1 of Cycles 1 through 3 (21 Day Cycles)]

### Eligibility Module

**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
* 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.

**Maximum Age:** 20 Years

**Minimum Age:** 0 Years

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ClinicalTrials.gov@lilly.com

**Name:** There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

**Phone:** 317-615-4559

**Role:** CONTACT

**Contact 2:**

**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)

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Phoenix

**Contacts:**

***Contact 1:***

- **Name:** Lindsey M Hoffman

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Phoenix Childrens Hospital (PCH)

**State:** Arizona

**Zip:** 97557

#### Overall Officials

**Official 1:**

**Affiliation:** Eli Lilly and Company

**Name:** Contact Lilly at 1-800-LillyRx (1-800-545-5979)

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**Access Criteria:** A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

**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.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- CSR

**IPD Sharing:** YES

**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.

**URL:** http://vivli.org/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9020

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: M5209

- Name: Brain Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M15917

- Name: Spinal Cord Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T2519

- Name: Glioma

- Relevance: HIGH

- As Found: Glioma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005910

- Term: Glioma

### Intervention Browse Module - Ancestors

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000000477

- Term: Alkylating Agents

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1692

- Name: Temozolomide

- Relevance: HIGH

- As Found: Head

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077204

- Term: Temozolomide

### Misc Info Module

- Version Holder: 2024-05-31
