Clinical Trials /

Abemaciclib in Patients With Oligodendroglioma

NCT03969706

Description:

This is a phase II, single arm, open label study looking how well a drug called abemaciclib works in patients with recurrent oligodendroglioma

Related Conditions:
  • Oligodendroglioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib in Patients With Oligodendroglioma
  • Official Title: A Single-Arm, Open-label, Phase II Study Evaluating the Efficacy and Safety of Abemaciclib in Patients With Recurrent Oligodendroglioma

Clinical Trial IDs

  • ORG STUDY ID: UPCC 28318
  • NCT ID: NCT03969706

Conditions

  • Oligodendroglioma, Adult

Interventions

DrugSynonymsArms
Abemaciclib 200 MGSingle Arm

Purpose

This is a phase II, single arm, open label study looking how well a drug called abemaciclib works in patients with recurrent oligodendroglioma

Detailed Description

      Primary Objective:

      • To determine the efficacy of abemaciclib for recurrent oligodendroglioma, as measured by
      the estimated proportion of patients alive without disease progression at 6 months from study
      enrollment (PFS-6)

      Secondary Objectives:

        -  To evaluate the safety and tolerability of abemaciclib in recurrent oligodendroglioma

        -  To estimate the objective radiographic response rate (ORR) associated with abemaciclib
           in recurrent oligodendroglioma

        -  To determine the median progression-free survival (PFS) and overall survival (OS) of
           patients with recurrent oligodendroglioma treated with abemaciclib

        -  To determine ORR, PFS, and OS in the subgroup of recurrent oligodendroglioma patients
           with tumor CIC gene mutations

      Exploratory Objectives:

        -  To measure pharmacodynamic markers of abemaciclib activity on oligodendroglial tumor
           cells

        -  To identify pre-treatment tumor characteristics that are associated with response to
           abemaciclib recurrent oligodendroglioma
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalAbemaciclib 200mg tablet PO twice daily administered on 28-day cycles Subjects remain on treatment until tumor progression or unacceptable toxicity.
  • Abemaciclib 200 MG

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically and molecularly confirmed diagnosis of oligodendroglioma according to
             2016 WHO Classification (tumor tissue must show co-deletion of chromosomes 1p and 19q,
             referred to as "1p/19q codeletion").

          2. Oligodendroglioma must be progressive or recurrent following BOTH a) prior radiation
             therapy and b) at least one prior line of alkylating chemotherapy.

          3. Patients must have measurable contrast-enhancing disease (defined by at least 1cm x
             1cm) by magnetic resonance imaging (MRI) imaging within 21 days of starting treatment

          4. Patients may have had treatment for an unlimited number of prior relapses.. Recent
             surgical resection for recurrence is allowed, as long as there remains measurable
             contrast-enhancing disease after surgery.

          5. Patients must have recovered from severe toxicity of prior therapy. Patients who
             received chemotherapy must have recovered (Common Terminology Criteria for Adverse
             Events [CTCAE v. 5.0] Grade ≤1) from the acute effects of chemotherapy except for
             residual alopecia or grade 2 peripheral neuropathy prior to enrollment. The following
             intervals from previous treatments are required to be eligible:

               -  12 weeks from the completion of radiation

               -  6 weeks from a nitrosourea cytotoxic chemotherapy

               -  3 weeks from a non-nitrosourea cytotoxic chemotherapy

               -  4 weeks from any investigational (not Food and Drug Administration [FDA]-approved
                  for oligodendroglioma or other gliomas) agents

          6. Patients must be able to swallow oral medications

          7. Age 18 or older

          8. Karnofsky performance status >= 60

          9. Life expectancy >3 months

         10. Adequate hematologic parameters, including:

               -  Absolute neutrophil count >= 1,500/ul

               -  Platelets >= 100,000/ul

               -  Hemoglobin >= 8 g/dl. Patients may receive erythrocyte transfusions to achieve
                  this hemoglobin level at the discretion of the investigator. Initial treatment
                  must not begin earlier than the day after the erythrocyte transfusion.

         11. Adequate hepatic function within 7 days prior to enrollment, defined as follows

               -  Total bilirubin ≤ 1.5 x ULN (patients with Gilbert's Syndrome with a total
                  bilirubin ≤ 2.0 mg/dl and direct bilirubin within normal limits are permitted)

               -  ALT and AST ≤ 3x upper limit of normal (ULN)

         12. Adequate renal function within 7 days prior to enrollment, defined as follows:

               -  serum creatinine <=1.5 x institutional ULN OR calculated creatinine clearance
                  (glomerular filtration rate can also be used in place of creatinine or CrCl) >=50
                  mL/min for subjects with creatinine levels >1.5x institutional ULN

        Exclusion Criteria:

        Any of the following would exclude the subject from participation in the study:

          1. Prior treatment with a CDK4/6 inhibitor

          2. Patients must not be on enzyme-inducing anti-epileptic drugs (EIAEDs; carbamazepine,
             phenytoin, and phenobarbitol)

          3. The patient has serious preexisting medical condition(s) that would preclude
             participation in this study (for example, interstitial lung disease, severe dyspnea at
             rest or requiring oxygen therapy, history of major surgical resection involving the
             stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
             preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)

          4. Females who are pregnant or lactating are excluded.

               -  If a female of childbearing potential, must have a negative serum pregnancy test
                  within 7 days of the first dose of abemaciclib and agree to use a medically
                  approved contraceptive method during the treatment period and for 3 months
                  following the last dose of abemaciclib.

               -  If a male, agree to use a reliable method of birth control and to not donate
                  sperm during the treatment period and for at least 3 months following the last
                  dose of abemaciclib.

               -  Contraceptive methods may include an intrauterine device [IUD] or barrier method.
                  If condoms are used as a barrier method, a spermicidal agent should be added as a
                  double barrier protection.

               -  Women must agree not to breast feed while on abemaciclib treatment and for at
                  least three months following the last dose of study therapy.

          5. The patient has active bacterial infection (requiring intravenous [IV] antibiotics at
             time of initiating study treatment), fungal infection, or detectable viral infection
             (such as known human immunodeficiency virus positivity or with known active hepatitis
             B or C). Patients with known HIV infection are excluded given the potential for
             interactions between antiretroviral agents and abemaciclib. Patients with known
             Hepatitis B or Hepatitis C infection are excluded only if there is evidence of active
             infection (detectable Hepatitis B surface antigen, detectable Hepatitis C RNA). For
             patients without known viral hepatitis or HIV infection, viral hepatitis and HIV
             testing are NOT required to determine eligibility for this trial.

          6. The patient has a personal history of any of the following conditions: syncope of
             cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but
             not limited to, ventricular tachycardia and ventricular fibrillation), or sudden
             cardiac arrest.

          7. Subjects with major medical, neurologic or psychiatric condition who are judged as
             unable to fully comply with study therapy or assessments should not be enrolled.

          8. Prisoners or subjects who are involuntarily incarcerated are excluded.

          9. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness are excluded

         10. Subjects requiring concurrent administration of any other anticancer agents including
             chemotherapy and biologic agents (such as bevacizumab) or the use of other concurrent
             investigational treatment drugs and/or devices.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:6 months after initiation of study therapy
Safety Issue:
Description:Assessed as a) Tumor progression (as measured by modified RANO criteria) or death due to disease or toxicity; OR b) alive without tumor progression

Secondary Outcome Measures

Measure:Safety and tolerability of this therapy
Time Frame:From initiation of study drug to 28 days after the end of treatment visit
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0
Measure:Objective radiographic response (ORR)
Time Frame:Up to 2 years
Safety Issue:
Description:measured by modified Response Assessment in Neuro-Oncology (RANO) criteria.
Measure:Progression Free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:defined as the time from date of enrollment until the earliest date of disease progression (as determined by modified RANO criteria) or death due to any cause
Measure:Overall Survival
Time Frame:From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Safety Issue:
Description:defined as the time from date of enrollment until death from any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

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