Vestibular SchwannomaEarly Phase 1NCT02282917
Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
A Early Phase 1 study testing AR-42 in people with Vestibular Schwannoma and Meningioma, run by Massachusetts Eye and Ear Infirmary at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Vestibular Schwannoma, Meningioma, Acoustic Neuroma
- What is being tested?
- AR-42
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 4 sitesUnited States
- Study dates
- Dec 2015to 4 Jan 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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
Who cannot join
- 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.
Show all 19Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Johns Hopkins University
Baltimore, Maryland, 21287
Massachusetts Eye and Ear
Boston, Massachusetts, 02214
Mayo Clinic
Rochester, Minnesota, 55905
Stanford University
Stanford, California, 94305
About this study
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.
Read the detailed description
This is a multi-center, proof of concept phase 0 study to assess the suppression of p-AKT in VS and meningiomas by AR-42 in adult patients undergoing NF2-tumor resection. AR-42 will be administered three times per week beginning 3 weeks prior to surgery. A total of ten doses, +/- 1 dose at 40 mg/dose, will be self-administered orally by study participants at approximately the same time every day (+/- 1 hour, preferably in the evening) 3 times per week for 3 weeks pre-operatively, with the last dose taken the night before surgery. Patients will be evaluated within the context of their standard post-operative follow up which includes within 2 days of surgery and again at 2 weeks (+/- 10 days) after surgery. Samples will be shipped to the participating laboratories (OSU Comprehensive Cancer Center (CCC) Pharmacoanalytical Shared Resource (PhASR) and Nationwide Children's Research Institute) for assessment of intratumoral drug concentration and assessment of intratumoral disease markers. During surgery, four blood samples will also be obtained and sent to the cooperating laboratory (PhASR) for determination of drug concentration and molecular analysis.
- Being tested
- AR-42
- Keywords
- NF2, Vestibular Schwannoma, Schwannoma, Meningioma
- Medical subject headings
- Neuroma, Acoustic, Meningioma, Neurofibromatosis 2, Neurilemmoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AR-42Drug
Also called OSU-HDAC42
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.
| Study group | Role | What they receive |
|---|---|---|
| AR-42 Administration | Experimental | AR-42 will be administered three times per week beginning 3 weeks prior to surgery. Receives: Drug: AR-42 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ratio of Phospho-AKT (p-AKT) to AKT After 3 Weeks of Oral AR-42
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.
Measured: 3 weeks
Peripheral Phospho-AKT (p-AKT) to AKT Ratio After 3 Weeks of Oral AR-42
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.
Measured: 3 weeks
Secondary outcomes (5)
AR-42 Plasma Concentration
Steady-state plasma concentrations of AR-42 at the time of tumor resection are provided.
Measured: 1 week
AR-42 Tumor Concentration (Capsule)
Concentrations of AR-42 at the tumor capsule are provided.
Measured: 1 week
AR-42 Tumor Concentration (Center)
Intra-tumor concentrations of AR-42 at the tumor center are reported.
Measured: 1 week
AR-42 Tumor Concentration (Capsule/Plasma)
Capsule/plasma intra-tumor AR-42 concentrations are provided as a ratio.
Measured: 1 week
AR-42 Tumor Concentration (Center/Plasma)
Center/plasma intra-tumoral AR-42 concentrations are provided as a ratio.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startDec 2015
- Primary completion30 May 2017
- Study completion4 Jan 2021
Why it stopped: Drug manufacturing logistics; lack of access to drug supply
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Vestibular SchwannomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Stanford University, Ohio State University, Nationwide Children's Hospital, Mayo Clinic
- Responsible party
- Principal investigator, D. Bradley Welling, MD, PhD, Massachusetts Eye and Ear Infirmary
- Investigators
- Brad Welling, MD, PhD, Principal investigator, Massachusetts Eye and Ear
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282917
- Sponsor's protocol ID
- 14-078H
- Status last verified
- Oct 2026
- First submitted
- 31 Oct 2014
- Last updated
- 28 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Welling DB, Collier KA, Burns SS, Oblinger JL, Shu E, Miles-Markley BA, Hofmeister CC, Makary MS, Slone HW, Blakeley JO, Mansouri SA, Neff BA, Jackler RK, Mortazavi A, Chang LS. Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas. Laryngoscope Investig Otolaryngol. 2021 Aug 20;6(5):1008-1019. doi: 10.1002/lio2.643. eCollection 2021 Oct.
PubMed 34667843Cheng H, Xie Z, Jones WP, Wei XT, Liu Z, Wang D, Kulp SK, Wang J, Coss CC, Chen CS, Marcucci G, Garzon R, Covey JM, Phelps MA, Chan KK. Preclinical Pharmacokinetics Study of R- and S-Enantiomers of the Histone Deacetylase Inhibitor, AR-42 (NSC 731438), in Rodents. AAPS J. 2016 May;18(3):737-45. doi: 10.1208/s12248-016-9876-3. Epub 2016 Mar 4.
PubMed 26943915
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma
- ClinicalTrials.gov ID
- NCT02282917
- Acronym / sponsor ID
- 14-078H
- Keywords
- NF2, Vestibular Schwannoma, Schwannoma, Meningioma
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug manufacturing logistics; lack of access to drug supply
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Collaborators
- Johns Hopkins University, Stanford University, Ohio State University, Nationwide Children's Hospital, Mayo Clinic
- Study start
- Dec 2015 (actual)
- Primary completion
- 30 May 2017 (actual)
- Study completion
- 4 Jan 2021 (actual)
- First posted
- 5 Nov 2014 (estimated)
- Results
- Posted 11 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multi-center, proof of concept phase 0 study to assess the suppression of p-AKT in VS and meningiomas by AR-42 in adult patients undergoing NF2-tumor resection. AR-42 will be administered three times per week beginning 3 weeks prior to surgery. A total of ten doses, +/- 1 dose at 40 mg/dose, will be self-administered orally by study participants at approximately the same time every day (+/- 1 hour, preferably in the evening) 3 times per week for 3 weeks pre-operatively, with the last dose taken the night before surgery. Patients will be evaluated within the context of their standard post-operative follow up which includes within 2 days of surgery and again at 2 weeks (+/- 10 days) after surgery. Samples will be shipped to the participating laboratories (OSU Comprehensive Cancer Center (CCC) Pharmacoanalytical Shared Resource (PhASR) and Nationwide Children's Research Institute) for assessment of intratumoral drug concentration and assessment of intratumoral disease markers. During surgery, four blood samples will also be obtained and sent to the cooperating laboratory (PhASR) for determination of drug concentration and molecular analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AR-42 Administration | Experimental | Drug: AR-42AR-42 will be administered three times per week beginning 3 weeks prior to surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AR-42Also: OSU-HDAC42AR-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. | Drug | AR-42 Administration |
Primary outcome
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.
5 secondary outcomes
AR-42 Plasma Concentration
Time frame: 1 week
AR-42 Tumor Concentration (Capsule)
Time frame: 1 week
AR-42 Tumor Concentration (Center)
Time frame: 1 week
AR-42 Tumor Concentration (Capsule/Plasma)
Time frame: 1 week
AR-42 Tumor Concentration (Center/Plasma)
Time frame: 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34667843Welling DB, Collier KA, Burns SS, Oblinger JL, Shu E, Miles-Markley BA, Hofmeister CC, Makary MS, Slone HW, Blakeley JO, Mansouri SA, Neff BA, Jackler RK, Mortazavi A, Chang LS. Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas. Laryngoscope Investig Otolaryngol. 2021 Aug 20;6(5):1008-1019. doi: 10.1002/lio2.643. eCollection 2021 Oct.
- Derived from this study: PubMed 26943915Cheng H, Xie Z, Jones WP, Wei XT, Liu Z, Wang D, Kulp SK, Wang J, Coss CC, Chen CS, Marcucci G, Garzon R, Covey JM, Phelps MA, Chan KK. Preclinical Pharmacokinetics Study of R- and S-Enantiomers of the Histone Deacetylase Inhibitor, AR-42 (NSC 731438), in Rodents. AAPS J. 2016 May;18(3):737-45. doi: 10.1208/s12248-016-9876-3. Epub 2016 Mar 4.
- Individual participant dataSharing planned: No
Related trials for Vestibular Schwannoma
Enrolling by invitationObservational study
Long Term Follow-up Study of AAVAnc80-antiVEGF Gene Therapy
Vestibular Schwannoma
RecruitingPhase 1/2
Anti-VEGF Gene Therapy Trial for Vestibular Schwannoma
Vestibular Schwannoma
Not yet recruitingPhase 2
Selumetinib for NF2-Related Schwannomatosis
Neurofibromatosis Type 2, NF2
RecruitingPhase 2
Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
Neurofibromatosis Type 2, Vestibular Schwannoma
RecruitingPhase 3
Steroids for Facial Nerve Function Protection in Post-surgical Vestibular Schwannoma Patients
Vestibular Schwannoma, Facial Nerve Paralysis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brad Welling, MD, PhD principal investigator
Massachusetts Eye and Ear
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing AR-42 in people with Vestibular Schwannoma and Meningioma, run by Massachusetts Eye and Ear Infirmary at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ratio of Phospho-AKT (p-AKT) to AKT After 3 Weeks of Oral AR-42 (time frame: 3 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02282917, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.