Abemaciclib w/Bevacizumab in Recurrent GBM Pts w/Loss of CDKN2A/B or Gain or Amplification of CDK4/6

NCT04074785 | Terminated Early Phase 1 DMC FDA Drug

• 1 other identifier: STU-2019-1214
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Describe the safety and adverse events associated with Abemaciclib 150 mg orally twice daily when administered with Bevacizumab 10 mg/kg intravenously every 2 weeks to recurrent GBM patients with specific tumor molecular aberrations

Conditions

GBM; Glioblastoma; Brain Tumor; Brain Tumor, Recurrent

Keywords

Abemaciclib; Bevacizumab; CDKN2A/B; CDK4/6; Verzenio; Avastin

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse event

  Assess safety and adverse events associated with Abemaciclib 150 mg orally twice daily when administered with Bevacizumab 10 mg/kg intravenously every 2 weeks to recurrent GBM patients with specific tumor molecular aberrations. NCI Common terminology criteria for adverse events (CTCAE v.5) will be used to assess the adverse events.

  upto 2 years after study treatment

Secondary Outcomes (2)

• Median Overall Survival

  upto 2 years after study treatment

• Median Progression Free Survival

  upto 2 years after study treatment

Study Arms (2)

Safety Run-In

EXPERIMENTAL

Abemaciclib 150 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles

Drug: Abemaciclib; Drug: Bevacizumab

Abemaciclib with Bevacizumab

EXPERIMENTAL

Abemaciclib 100 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles

Drug: Abemaciclib; Drug: Bevacizumab

Interventions

Abemaciclib DRUG

Abemaciclib 150 mg po bid

Also known as: Verzenio

Abemaciclib with Bevacizumab; Safety Run-In

Bevacizumab DRUG

Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles

Also known as: Avastin

Abemaciclib with Bevacizumab; Safety Run-In

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed GBM at first or second recurrence after concurrent chemoradiotherapy. Patients with an initial diagnosis of a lower-grade glioma are eligible if a subsequent biopsy was determined to be GBM. GBMs either from the initial resection or at repeat resection at recurrence must be analyzed by next-generation exome sequencing (NES) and RNA-sequencing and must have the following aberrations:
• Heterozygous or homozygous loss of CDKN2A and/or CDKN2B
• Gain or amplification of CDK4 and/or 6
• NOTE: Patients with GBMs having loss of function of RB1 are EXCLUDED.
• Imaging confirmation of first tumor progression or regrowth as defined by the RANO criteria. A minimum of 12 weeks must have elapsed from the completion of radiotherapy to study entry to minimize the potential for magnetic resonance imaging (MRI) changes related to radiation necrosis that might be misdiagnosed as progression of disease, unless there is a new lesion outside the radiation field or unequivocal evidence of viable tumor on histopathological sampling.
• Karnofsky performance status (KPS) ≥ 60%.
• Stable or decreasing dose of corticosteroids within 5 days prior to randomization.
• For women who are of child-bearing potential or surgically sterile (absence of ovaries and/or uterus) and who are sexually active: to use an adequate method of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the treatment period and for at least 6 months after last dose of study drug. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• For male patients who are partners of premenopausal women: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug.
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Patients who have undergone recent surgery for recurrent or progressive tumor are eligible provided that:
• Surgery must have confirmed the recurrence.
• A minimum of 28 days must have elapsed from the day of surgery to study entry. For core or needle biopsy, a minimum of 7 days must have elapsed prior to study entry.

You may not qualify if:

• Prior treatment with Bevacizumab, Abemaciclib, or any other CDK4/6 inhibitor or other systemic VEGF- or VEGF-receptor-targeted agent.
• Prior treatment with prolifeprospan 20 with carmustine wafer.
• Evidence of recent hemorrhage on baseline MRI of the brain. However, patients with clinically asymptomatic presence of hemosiderin, resolving hemorrhagic changes related to surgery, or presence of punctuate hemorrhage in the tumor are eligible.
• Concurrent investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Agent(s) or other agents used in study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Patients unable to undergo brain MRI scans with IV gadolinium.
• Screening laboratory values outside of the values listed on Table 2.
• Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg while on antihypertensive medication).
• Uncontrolled diabetes despite maximal medical management.
• Prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association Grade II or greater congestive cardiac failure.
• History of myocardial infarction (within 12 months) or unstable angina (within 6 months) prior to study entry.
• History of stroke or transient ischemic attacks within 6 months prior to study entry.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

abemaciclib; Bevacizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSISTANT PROFESSOR

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: August 30, 2019
• Study Start: December 13, 2019
• Primary Completion: October 16, 2023
• Study Completion: October 16, 2023
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

US (1)