Clinical Trials /

Pilot Study of Abemaciclib With Bevacizumab in Recurrent Glioblastoma Patients With Loss of CDKN2A/B or Gain or Amplification of CDK4/6

NCT04074785

Description:

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

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Abemaciclib With Bevacizumab in Recurrent Glioblastoma Patients With Loss of CDKN2A/B or Gain or Amplification of CDK4/6
  • Official Title: Pilot Study of Abemaciclib With Bevacizumab in Recurrent Glioblastoma Patients With Loss of CDKN2A/B or Gain or Amplification of CDK4/6

Clinical Trial IDs

  • ORG STUDY ID: SCCC-06319; STU-2019-1214
  • NCT ID: NCT04074785

Conditions

  • GBM
  • Glioblastoma
  • Brain Tumor
  • Brain Tumor, Recurrent

Interventions

DrugSynonymsArms
AbemaciclibVerzenioAbemaciclib with Bevacizumab
BevacizumabAvastinAbemaciclib with Bevacizumab

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Safety Run-InExperimentalAbemaciclib 150 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles
  • Abemaciclib
  • Bevacizumab
Abemaciclib with BevacizumabExperimentalAbemaciclib 100 mg po bid PLUS Bevacizumab 10 mg/kg IV every 2 weeks, then continue treatments for 2 cycles
  • Abemaciclib
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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

        OR

          -  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.

          -  Craniotomy or intracranial biopsy site must be adequately healed and free of drainage
             or cellulitis, and the underlying cranioplasty must appear intact at the time of
             randomization.

          -  Patients must be willing and able to provide written informed consent and to comply
             with the study protocol as judged by the investigator.

          -  Age ≥ 18 years.

          -  Patients must have recovered (Common Terminology Criteria for Adverse Events CTCAE]
             Grade ≤1) from the acute effects of chemotherapy prior to study entry. Minimum times
             from prior therapies include:

          -  ≥ 28 days elapsed from the administration of any investigational agent

          -  ≥ 28 days elapsed from the administration of any prior cytotoxic agents, except ≥ 42
             days from nitrosoureas

        NOTE: Prior treatment with Novo-TTF therapy is allowed at initial diagnosis, but must be
        discontinued prior to study entry.

          -  Patients must be able to swallow oral medications.

          -  Ability to understand and the willingness to sign a written informed consent.

          -  Patients must have adequate organ and marrow function

        Exclusion Criteria:

          -  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.

          -  Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent
             peripheral arterial thrombosis) within 6 months prior to study entry.

          -  Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
             anticoagulation).

          -  History of abdominal fistula or gastrointestinal perforation within 6 months prior to
             study entry.

          -  History of intracranial abscess within 6 months prior to randomization or active
             bacterial infection (requiring intravenous [IV] antibiotics within 2 weeks from
             initiation of study treatment), fungal infection, or detectable viral infection (such
             as known human immunodeficiency virus positivity or with known active hepatitis B or C
             [for example, hepatitis B surface antigen positive].

          -  Serious non-healing wound, active ulcer, or untreated bone fracture.

          -  History of another malignancy in the previous 3 years, with a disease-free interval of
             < 3 years. Patients with prior history of in situ cancer or basal or squamous cell
             skin cancer are ELIGIBLE.

          -  Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or
             humanized antibody.

          -  Taking any treatments listed in the Prohibited Concomitant Medications.
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety
Time Frame:2 years
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:To determine the median OS of the study patients from time of study entry until death or lost to follow-up.
Measure:Progression Free Survival
Time Frame:2 years
Safety Issue:
Description:To determine the median PFS of the study patients from time of study entry until progression as determined by the Response Assessment in Neuro-Oncology (RANO) criteria [30].

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Texas Southwestern Medical Center

Trial Keywords

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

Last Updated

January 6, 2020