A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma

Description

Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781/Abexinostat with metronomic temozolomide.

Conditions

Recurrent High Grade Glioma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Glioblastoma, Gliosarcoma

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Study Overview

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Study Details

Study overview

Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781/Abexinostat with metronomic temozolomide.

A Phase I Study of Metronomic Temozolomide With Abexinostat (PCI-24781) for Patients With Recurrent High Grade Glioma

A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma

Condition
Recurrent High Grade Glioma
Intervention / Treatment

-

Contacts and Locations

Omaha

University of Nebraska Medical Center, Omaha, Nebraska, United States, 68198

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Pathologically proven diagnosis of high grade (aka grade III or IV) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma)
  • * Prior radiation therapy and standard temozolomide; additional therapies for previous progressions are eligible (prior bevacizumab and Optune are allowed)
  • * Three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
  • * 19 years of age or older (the age of consent in Nebraska)
  • * Fully recovered from any toxicity of prior therapy that, in the opinion of the investigator, could impact tolerance to the study drug
  • * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • * Adequate bone marrow reserve (ANC count ≥1,500/mm3, hemoglobin \> 8 g/dL, platelet count ≥100,000/mm3)
  • * Adequate renal function (a serum creatinine that is at or below 2.0 mg/dL)
  • * Adequate hepatic function (serum AST and ALT less than 1.5 times the upper limits of normal, serum alkaline phosphatase less than 2.5 times the upper limits of normal)
  • * Able to provide written, informed consent
  • * Females of child-bearing potential must have a negative pregnancy test within 7 days of initiating study (non-child bearing potential is defined as age 55 years or older and no menses for two years or any age with surgical removal of the uterus and/or both ovaries)
  • * Females of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and up to 6 months following treatment
  • * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of oral PCI-24781/Abexinostat, or put the study outcomes at undue risk
  • * Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmia, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • * Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • * Immunotherapy, chemotherapy, radiotherapy, corticosteroids (at dosages equivalent to prednisone \> 20 mg/day) or experimental therapy (other than PCI-24781/Abexinostat PO) within 4 weeks before first dose of study drug
  • * Concurrent use of enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, felbamate, topiramate and oxcarbazepine)
  • * Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer
  • * Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection (no testing is required for eligibility)
  • * Creatinine \> 1.5 x institutional upper limit of normal (ULN); total bilirubin \> 1.5 x ULN (unless from Gilbert's disease), and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.5 x ULN
  • * Pregnant or breast-feeding
  • * Baseline ECG duration of the ventricular action potential corrected for heart rate (QTc interval) prolongation based on Fridericia's formula is \> 450 ms in males and \> 470 ms in females
  • * Concomitant valproic acid use, or another histone deacetylases (HDAC) inhibitor
  • * Receiving treatment with following medications and unable to discontinue treatment or switch medications prior to study enrollment:
  • * Amiodarone (Cordarone, Pacerone)
  • * Arsenic trioxide (Trisenox)
  • * Chlorpromazine (Aralen)
  • * Cisapride (Propulsid)
  • * Clarithromycin (Biaxin)
  • * Disopyramide (Norpace)
  • * Dofetilide (Tikosyn)
  • * Doperidol (Inapsine)
  • * Erythromycin (EryTab, Erythrocin)
  • * Flecanide (Tambocor)
  • * Haloperidol (Haldol)
  • * Ibutilide (Corvert)
  • * Methadone (Methadose, Dolophine)
  • * Moxifloxacin (Avelox)
  • * Pentamidine (Pentam, Nebupent)
  • * Pimozide (Orap)
  • * Procainamide (Procan, Pronestyl)
  • * Quinidine (Cardioquin, Quinaglute)
  • * Sotalol (Betapace)
  • * Thioridazine (Mellaril)
  • * Vandetanib (Zactima)

Ages Eligible for Study

19 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Nebraska,

Nicole A Shonka, MD, PRINCIPAL_INVESTIGATOR, University of Nebraska

Study Record Dates

2027-03