Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma

Not Recruiting

Trial ID: NCT02282917


This will be a multi-center, proof of concept phase 0 study to assess the suppression of p-AKT in Vestibular Schwannoma (VS) and meningiomas by AR-42 in adult patients undergoing tumor resection. AR-42 is a small molecule which crosses the blood brain barrier (BBB) in rodents, but the investigators are not certain yet if it will penetrate human VS. Meningiomas are outside the BBB, but seem to be unusually resistant to all current medical treatments. The primary endpoint of the bioactivity of suppression of p-AKT by AR-42 was selected as drug activity seems more informative than bioavailability. Our preclinical data and others have shown dose dependent suppression of p-AKT by AR-42 in both VS and meningiomas.

Official Title

Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma

Stanford Investigator(s)

Nikolas Blevins, MD
Nikolas Blevins, MD

Larry and Sharon Malcolmson Professor in the School of Medicine, Professor of Otolaryngology - Head & Neck Surgery (OHNS) and, by courtesy, of Neurosurgery

Paul D. Blumenthal, MD, MPH
Paul D. Blumenthal, MD, MPH

Professor of Obstetrics and Gynecology (Gynecology-Family Planning) at the Stanford University Medical Center, Emeritus

Donald E. Born
Donald E. Born

Clinical Professor, Pathology


Inclusion Criteria:

   - Patients with vestibular schwannoma and/or meningioma diagnosed by MRI where surgical
   resection has been selected as treatment.

   - Patients diagnosed with NF2 must meet Manchester Criteria.

   - Age > 18 years of age

   - Prior biologic therapy, chemotherapy, surgery or radiation is permitted.

   - At the time of screening, the patient must have normal organ and marrow function.

   - Eastern Cooperative Oncology Group/World Health Organization (ECOG/WHO) performance
   status of 0-1.

   - Patients must be able to swallow capsules.

   - Patients or their legal representatives must be able to read, understand and provide
   informed consent to participate in the trial.

   - Tumor type will be confirmed by a neuropathologist.

   - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
   test with a sensitivity of at least 50 mIU/mL prior to starting AR-42.

   - The patient must be willing to comply with fertility requirements

Exclusion Criteria:

   - Pregnant women are excluded from this study because the potential for teratogenic or
   abortifacient effects of AR-42 are not known. Because there is an unknown but
   potential risk for AEs in nursing infants secondary to treatment of the mother with
   AR-42, breastfeeding should be discontinued if the mother is treated with AR-42.

   - Pediatric patients are excluded from the phase 0 study as the effects of AR-42 are not
   known on children and there is no potential direct benefit to them.

   - Patients with malabsorption or any other condition that in the opinion of the
   principal investigator could cause difficulty in absorption of drug.

   - Patients requiring chronic corticosteroids (dose equivalent > 20mg prednisolone).

   - Concurrent use of complementary or alternative medicines that in the opinion of the
   principal investigator would confound the interpretation of toxicities and/or
   antitumor activity of the study drug.

   - Patients with a "currently active" second malignancy that, in the opinion of the
   principal investigator, will interfere with patient participation, increase patient
   risk, or confound data interpretation.

   - Patients with a mean QTcB > 450 msec in males and > 470 msec in females.

   - Patients with long QT syndrome.

   - Patients who are being treated for an active infection.

   - Patients receiving the following concomitant medications:

      - Any other anti-neoplastic chemotherapy or biologic therapy during the study

      - Concomitant radiotherapy

      - Concomitant HDAC inhibitors (e.g. valproic acid) as class-specific adverse
      reactions may be additive

      - Use of granulocyte colony-stimulating factors including G-CSF, pegylated G-CSF or
      GM-CSF should follow ASCO guidelines for patients receiving anti-cancer therapy.

      - Drugs associated with QT/QTc prolongation (see Appendix A)

   - Patients who are receiving concurrent anti-neoplastic therapy.

   - Any other medical condition, including mental illness or substance abuse, deemed by
   the principal investigator to likely interfere with a patient's ability to sign
   informed consent, cooperate and participate in the study, or interfere with the
   interpretation of the results.

   - Patients with significant cardiovascular disease, including a myocardial infarction or
   unstable angina within 6 months or unstable cardiac arrhythmias are not eligible for
   the study.

   - Known HIV infection, as their immunosuppressive conditions may complicate potential
   pancytopenias seen with HDAC inhibitors and complicate evaluation of drug effect.


drug: AR-42

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Robert Jackler, MD