Abemaciclib in Treating Patients with Recurrent Oligodendroglioma

Status: Active

Description

This phase II trial studies how well abemaciclib works in treating patients with oligodendroglioma that has come back after previous treatment. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Histologically and molecularly confirmed diagnosis of oligodendroglioma according to 2016 World Health Organization (WHO) classification (tumor tissue must show co-deletion of chromosomes 1p and 19q, referred to as “1p/19q codeletion”). * Acceptable methods for determination of 1p/19q codeletion include fluorescent in situ hybridization (FISH), genomic sequencing, or methylomic analyses; testing must have been performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory. * Tumors may have been either grade II or grade III at time of initial diagnosis.
  • Patients must have a tumor tissue form indicating availability of archived tumor tissue from a previous surgery for oligodendroglioma, completed and signed by a pathologist.
  • Oligodendroglioma must be progressive or recurrent following BOTH a) prior radiation therapy and b) at least one prior line of alkylating chemotherapy. * Of 10 total subjects enrolled, at least 2 subjects must have had only one prior line of alkylating chemotherapy. It is acceptable that more than 2 subjects may have had only one prior line of alkylating chemotherapy, but if the study has reached 8 treated subjects who have had more than one prior line of alkylating chemotherapy, then the remaining 2 subjects enrolled must have had only one prior line. * Both previous radiotherapy and chemotherapy could have been received as initial adjuvant therapy or for previous recurrences, and both previous radiotherapy and chemotherapy could have been used when the tumor was grade II.
  • 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.
  • Patients may have had treatment for an unlimited number of prior relapses but must NOT have had prior bevacizumab. 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.
  • Karnofsky performance status >= 60.
  • Life expectancy > 3 months.
  • 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.
  • 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) (within 7 days prior to enrollment).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) (within 7 days prior to enrollment).
  • International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Exception allowed for patients receiving anti-coagulation treatment (within 7 days prior to enrollment).
  • Serum creatinine =< 1.5 x institutional ULN OR calculated creatinine clearance (glomerular filtration rate can also be used in place of creatinine or creatinine clearance [CrCl]) >= 50 mL/min for subjects with creatinine levels > 1.5 x institutional ULN (within 7 days prior to enrollment).

Exclusion Criteria

  • Prior treatment with a CDK4/6 inhibitor.
  • Patients with known or suspected leptomeningeal disease are excluded.
  • Patients must not be on enzyme-inducing anti-epileptic drugs (enzyme-inducing antiepileptic drugs [EIAEDs]; carbamazepine, phenytoin, and phenobarbital).
  • 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 human immunodeficiency virus (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 ribonucleic acid [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 (e.g., infectious disease) illness are excluded.
  • Subjects requiring 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.

Locations & Contacts

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Contact: Stephen Joseph Bagley
Phone: 215-614-1858
Email: Stephen.Bagley@uphs.upenn.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. 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:

I. To evaluate the safety and tolerability of abemaciclib in recurrent oligodendroglioma.

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

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

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

EXPLORATORY OBJECTIVES:

I. To measure pharmacodynamic markers of abemaciclib activity on oligodendroglial tumor cells.

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

OUTLINE:

Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and every 10-12 weeks thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pennsylvania / Abramson Cancer Center

Principal Investigator
Stephen Joseph Bagley

Trial IDs

Primary ID UPCC 28318
Secondary IDs NCI-2019-03149
Clinicaltrials.gov ID NCT03969706