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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02282917
• Date of registration: 31/10/2014
• Prospective Registration: Yes
• Primary sponsor: Massachusetts Eye and Ear Infirmary
• Public title: Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
• Scientific title: Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
• Date of first enrolment: September 2015
• Target sample size: 5
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02282917
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Early Phase 1

Countries of recruitment

United States

Contacts

• Name: Brad Welling, MD, PhD
• Affiliation: Massachusetts Eye and Ear

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Vestibular Schwannoma

Acoustic Neuroma

Meningioma

Neurofibromatosis Type 2

Intervention(s)

Drug: AR-42

Primary Outcome(s)

Expression levels of phospho-Akt (p-AKT) and p16INKA after 3 weeks of oral AR-42 [Time Frame: 3 weeks]

Secondary Outcome(s)

Audiometric changes by conventional pure tone and speech discrimination testing [Time Frame: 6 weeks]

The utility of HR23B as a biomarker for sensitivity of VS and meningiomas [Time Frame: 1 week]

Biological effects on tumor proliferation (as assessed by Ki-67 proliferation index), etc. [Time Frame: 1 week]

Gene sequencing (tumor and germ-line DNA) [Time Frame: 1 week]

Steady-state plasma and intra-tumoral concentrations of AR-42 [Time Frame: 1 week]

Biological effects onPI3K (including levels of p-AKT, total AKT, p-PRAS-40, total PRAS-40, p-S6 ribosomal protein, and p-4E-BP-1) [Time Frame: 1 week]

Volumetric tumor reduction by magnetic resonance imaging. [Time Frame: 1 week]

Secondary ID(s)

14-078H

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Stanford University

Johns Hopkins University

Nationwide Children's Hospital

Mayo Clinic

Ohio State University