RECRUITING

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

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Conditions

Recurrent High Grade GliomaAnaplastic AstrocytomaAnaplastic OligodendrogliomaGlioblastomaGliosarcoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2023-06-26
Study Completion:2027-03
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05698524

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.

Ages Eligible for Study:19 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Pathologically proven diagnosis of high grade (aka grade III or IV) glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, glioblastoma, gliosarcoma)
  2. * Prior radiation therapy and standard temozolomide; additional therapies for previous progressions are eligible (prior bevacizumab and Optune are allowed)
  3. * Three or more months from the end of chemoradiotherapy or have biopsy or imaging consistent with disease progression
  4. * 19 years of age or older (the age of consent in Nebraska)
  5. * Fully recovered from any toxicity of prior therapy that, in the opinion of the investigator, could impact tolerance to the study drug
  6. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  7. * Adequate bone marrow reserve (ANC count ≥1,500/mm3, hemoglobin \> 8 g/dL, platelet count ≥100,000/mm3)
  8. * Adequate renal function (a serum creatinine that is at or below 2.0 mg/dL)
  9. * 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)
  10. * Able to provide written, informed consent
  11. * 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)
  12. * 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
  1. * 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
  2. * 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
  3. * 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
  4. * 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
  5. * Concurrent use of enzyme-inducing antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, felbamate, topiramate and oxcarbazepine)
  6. * Any other active malignancy other than nonmelanoma skin cancer or controlled prostate cancer
  7. * 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)
  8. * 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
  9. * Pregnant or breast-feeding
  10. * 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
  11. * Concomitant valproic acid use, or another histone deacetylases (HDAC) inhibitor
  12. * Receiving treatment with following medications and unable to discontinue treatment or switch medications prior to study enrollment:
  13. * Amiodarone (Cordarone, Pacerone)
  14. * Arsenic trioxide (Trisenox)
  15. * Chlorpromazine (Aralen)
  16. * Cisapride (Propulsid)
  17. * Clarithromycin (Biaxin)
  18. * Disopyramide (Norpace)
  19. * Dofetilide (Tikosyn)
  20. * Doperidol (Inapsine)
  21. * Erythromycin (EryTab, Erythrocin)
  22. * Flecanide (Tambocor)
  23. * Haloperidol (Haldol)
  24. * Ibutilide (Corvert)
  25. * Methadone (Methadose, Dolophine)
  26. * Moxifloxacin (Avelox)
  27. * Pentamidine (Pentam, Nebupent)
  28. * Pimozide (Orap)
  29. * Procainamide (Procan, Pronestyl)
  30. * Quinidine (Cardioquin, Quinaglute)
  31. * Sotalol (Betapace)
  32. * Thioridazine (Mellaril)
  33. * Vandetanib (Zactima)

Contacts and Locations

Study Contact

Michaela K Savine, RN
CONTACT
402-836-9488
misavine@unmc.edu

Principal Investigator

Nicole A Shonka, MD
PRINCIPAL_INVESTIGATOR
University of Nebraska

Study Locations (Sites)

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

Collaborators and Investigators

Sponsor: University of Nebraska

  • Nicole A Shonka, MD, PRINCIPAL_INVESTIGATOR, University of Nebraska

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-26
Study Completion Date2027-03

Study Record Updates

Study Start Date2023-06-26
Study Completion Date2027-03

Terms related to this study

Additional Relevant MeSH Terms

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