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Abemaciclib in Patients With Oligodendroglioma

Primary Purpose

Oligodendroglioma, Adult

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Abemaciclib 200 MG
Sponsored by
Stephen Bagley, MD, MSCE
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oligodendroglioma, Adult

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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 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.
  4. 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
  5. Patients must be able to swallow oral medications
  6. Age 18 or older
  7. Karnofsky performance status >= 60
  8. Life expectancy >3 months
  9. 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.
  10. 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)
  11. 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.

Sites / Locations

  • University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

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

Outcomes

Primary Outcome Measures

Progression-free survival
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

Safety and tolerability of this therapy
Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0
Objective radiographic response (ORR)
measured by modified Response Assessment in Neuro-Oncology (RANO) criteria.
Progression Free Survival
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
Overall Survival
defined as the time from date of enrollment until death from any cause

Full Information

First Posted
May 21, 2019
Last Updated
October 6, 2023
Sponsor
Stephen Bagley, MD, MSCE
Collaborators
Abramson Cancer Center at Penn Medicine, University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT03969706
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 15, 2019 (Actual)
Primary Completion Date
May 15, 2025 (Anticipated)
Study Completion Date
May 15, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stephen Bagley, MD, MSCE
Collaborators
Abramson Cancer Center at Penn Medicine, University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oligodendroglioma, Adult

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is an open-label, single-institution, single-arm phase II study of the efficacy and safety of abemaciclib in patients with recurrent oligodendroglioma.
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Arm Description
Abemaciclib 200mg tablet PO twice daily administered on 28-day cycles Subjects remain on treatment until tumor progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Abemaciclib 200 MG
Intervention Description
Subjects will be treated with abemaciclib 200mg by mouth once every 12 hours. Dosing will be continuous and administered on a 28-day cycle
Primary Outcome Measure Information:
Title
Progression-free survival
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
Time Frame
6 months after initiation of study therapy
Secondary Outcome Measure Information:
Title
Safety and tolerability of this therapy
Description
Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0
Time Frame
From initiation of study drug to 28 days after the end of treatment visit
Title
Objective radiographic response (ORR)
Description
measured by modified Response Assessment in Neuro-Oncology (RANO) criteria.
Time Frame
Up to 2 years
Title
Progression Free Survival
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
Time Frame
Up to 2 years
Title
Overall Survival
Description
defined as the time from date of enrollment until death from any cause
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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"). Oligodendroglioma must be progressive or recurrent following BOTH a) prior radiation therapy and b) at least one prior line of alkylating chemotherapy. 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. 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 Patients must be able to swallow oral medications Age 18 or older Karnofsky performance status >= 60 Life expectancy >3 months 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. 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) 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: Prior treatment with a CDK4/6 inhibitor Patients must not be on enzyme-inducing anti-epileptic drugs (EIAEDs; carbamazepine, phenytoin, and phenobarbitol) 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) 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. 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. 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. 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. Prisoners or subjects who are involuntarily incarcerated are excluded. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness are excluded 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Bagley, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Abemaciclib in Patients With Oligodendroglioma

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