Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
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ClinicalTrials.gov Identifier: NCT02282917 |
Recruitment Status :
Terminated
(Drug manufacturing logistics; lack of access to drug supply)
First Posted : November 5, 2014
Results First Posted : May 11, 2022
Last Update Posted : May 11, 2022
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Condition or disease | Intervention/treatment | Phase |
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Vestibular Schwannoma Meningioma Acoustic Neuroma Neurofibromatosis Type 2 | Drug: AR-42 | Early Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 7 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma |
Actual Study Start Date : | December 2015 |
Actual Primary Completion Date : | May 30, 2017 |
Actual Study Completion Date : | January 4, 2021 |

Arm | Intervention/treatment |
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Experimental: AR-42 Administration
AR-42 will be administered three times per week beginning 3 weeks prior to surgery.
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Drug: AR-42
AR-42 will be administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, will be self-administered by study participants at approximately 8:00pm (+/- 1 hour) for 3 weeks pre-operatively, with the last dose being administered the night before surgery. The treating surgeon will perform the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Other Name: OSU-HDAC42 |
- Ratio of Phospho-AKT (p-AKT) to AKT After 3 Weeks of Oral AR-42 [ Time Frame: 3 weeks ]The phospho-AKT/AKT ratio was used to estimate the activity of AKT, a kinase, at the core of resected tumors. Quantitation of the normalized p-AKT/AKT ratio is depicted as a percentage relative to the untreated VS2 set as 100%. For example, a value under 100% indicates a lower level of AKT activity relative to untreated VS2 tumors. Phosphorylated AKT, or phospho-AKT, is the activated form of AKT. These measurements were derived from the core of the resected tumors.
- Peripheral Phospho-AKT (p-AKT) to AKT Ratio After 3 Weeks of Oral AR-42 [ Time Frame: 3 weeks ]The phospho-AKT/AKT ratio was used to estimate the activity of AKT, a kinase, at the core of resected tumors. Quantitation of the normalized p-AKT/AKT ratio is depicted as a percentage relative to the untreated VS2 set as 100%. For example, a value under 100% indicates a lower level of AKT activity relative to untreated patients. Phosphorylated AKT, or phospho-AKT, is the activated form of AKT. These measurements were derived from the periphery of the resected tumors.
- AR-42 Plasma Concentration [ Time Frame: 1 week ]Steady-state plasma concentrations of AR-42 at the time of tumor resection are provided.
- AR-42 Tumor Concentration (Capsule) [ Time Frame: 1 week ]Concentrations of AR-42 at the tumor capsule are provided.
- AR-42 Tumor Concentration (Center) [ Time Frame: 1 week ]Intra-tumor concentrations of AR-42 at the tumor center are reported.
- AR-42 Tumor Concentration (Capsule/Plasma) [ Time Frame: 1 week ]Capsule/plasma intra-tumor AR-42 concentrations are provided as a ratio.
- AR-42 Tumor Concentration (Center/Plasma) [ Time Frame: 1 week ]Center/plasma intra-tumoral AR-42 concentrations are provided as a ratio.
- Number of Doses of AR-42 Received [ Time Frame: 3 weeks ]We report the average total number of doses of AR-42 taken per participant during this study.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
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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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02282917
United States, California | |
Stanford University | |
Stanford, California, United States, 94305 | |
United States, Maryland | |
Johns Hopkins University | |
Baltimore, Maryland, United States, 21287 | |
United States, Massachusetts | |
Massachusetts Eye and Ear | |
Boston, Massachusetts, United States, 02214 | |
United States, Minnesota | |
Mayo Clinic | |
Rochester, Minnesota, United States, 55905 |
Principal Investigator: | Brad Welling, MD, PhD | Massachusetts Eye and Ear |
Documents provided by D. Bradley Welling, MD, PhD, Massachusetts Eye and Ear Infirmary:
Responsible Party: | D. Bradley Welling, MD, PhD, Chief Otolaryngology Massachusetts Eye and Ear, Massachusetts Eye and Ear Infirmary |
ClinicalTrials.gov Identifier: | NCT02282917 |
Other Study ID Numbers: |
14-078H |
First Posted: | November 5, 2014 Key Record Dates |
Results First Posted: | May 11, 2022 |
Last Update Posted: | May 11, 2022 |
Last Verified: | December 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
NF2 Vestibular Schwannoma Schwannoma Meningioma |
Meningioma Neurofibromatoses Neurilemmoma Neuroma Neuroma, Acoustic Neurofibromatosis 2 Neoplasms, Nerve Tissue Neoplasms by Histologic Type Neoplasms Neoplasms, Vascular Tissue Meningeal Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Nervous System Diseases |
Neurofibroma Nerve Sheath Neoplasms Neoplastic Syndromes, Hereditary Neurocutaneous Syndromes Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Genetic Diseases, Inborn Peripheral Nervous System Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Cranial Nerve Neoplasms Vestibulocochlear Nerve Diseases Retrocochlear Diseases Ear Diseases |