A Randomized, Open-Label, Phase 2 Study Evaluating Abemaciclib inCombination With Temozolomide Compared to Temozolomide Monotherapy in Children and Young Adults With Newly Diagnosed High-Grade Glioma Following Radiotherapy
Scott Coven
Primary Investigator
Brief description of study
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.
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.
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.
Detailed description of study
What will happen during the study?
Experimental: Abemaciclib + Temozolomide - Arm A
Participants will receive abemaciclib administered orally in addition to temozolomide administered orally or intravenously (IV).
Active Comparator: Temozolomide - Arm B
Participants will receive temozolomide administered orally or IV.
Study participation could last approximately 11 months and possibly longer depending upon how the participant/tumor respond.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: High-Grade Glioma, Riley
-
Age: 20 years or below
-
Gender: All
- 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</li>
- Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment.
- A performance score of ≥60 using:
- Lansky scale for participants <16 years
- 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.
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</li>
- Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment.
- A performance score of ≥60 using:
- Lansky scale for participants <16 years
- 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.
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</li>
- Life expectancy of ≥8 weeks and deemed likely to complete at least 1 cycle of treatment.
- A performance score of ≥60 using:
- Lansky scale for participants <16 years
- 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.
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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: Lansky scale for participants <16 years 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.
