Trial Outcomes & Findings for Exploratory Evaluation of AR-42 Histone Deacetylase Inhibitor in the Treatment of Vestibular Schwannoma and Meningioma (NCT NCT02282917)

Last Updated: 2025-12-05

Results Overview

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.

Recruitment status

TERMINATED

Study phase

EARLY_PHASE1

Target enrollment

7 participants

Primary outcome timeframe

3 weeks

Results posted on

2025-12-05

Participant Flow

Seven participants were identified and recruited by the study investigators and/or study coordinators within the Department of Otolaryngology at Massachusetts Eye and Ear, Boston, MA. Participants were identified by their clinical history with vestibular schwannomas, meningiomas, cutaneous schwannomas, and/or Neurofibromatosis Type 2. The first enrollment took place in December 2015, and the final enrollment took place in July 2017.

Following all participant enrollments (consent), baseline procedures to determine eligibility included: complete blood count with differential and platelets, comprehensive metabolic panel, coagulation panel (PT/PTT), chest x-ray, neurological exam, pregnancy testing, 12-lead ECG, audiogram, and MRI (CPT 70553). Participants were terminated from the study after their baseline visit if they did not meet all eligibility requirements.

Participant milestones

Participant milestones
Measure	AR-42 Administration There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Overall Study STARTED	7
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	AR-42 Administration There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Overall Study Withdrawal by Subject	1
Overall Study Screen Failure/Not Eligible	1

Baseline Characteristics

Two participants were withdrawn from the study prior to baseline weight measurement.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AR-42 Administration n=5 Participants AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, and was 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. A study investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	54.9 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants
Weight	98.22 kilograms (kg) n=5 Participants • Two participants were withdrawn from the study prior to baseline weight measurement.
Prior tumor biopsy or debulking Yes	0 Participants n=5 Participants
Prior tumor biopsy or debulking No	5 Participants n=5 Participants
Relevant diagnosis Sporadic vestibular schwannoma	4 Participants n=5 Participants
Relevant diagnosis Sporadic meningioma	1 Participants n=5 Participants
ECOG Grade ECOG = 0	4 Participants n=5 Participants
ECOG Grade ECOG not assessed at baseline	1 Participants n=5 Participants
Baseline plasma concentration of AR-42	150.18 nanomolar (nM) n=1 Participants • Plasma concentrations of AR-42 at baseline (before tumor resection) are reported individually for each of the 5 participants.

PRIMARY outcome

Timeframe: 3 weeks

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Ratio of Phospho-AKT (p-AKT) to AKT After 3 Weeks of Oral AR-42	53.6 percent (%) Interval 19.0 to 105.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Peripheral Phospho-AKT (p-AKT) to AKT Ratio After 3 Weeks of Oral AR-42	61.2 percent (%) Interval 9.0 to 102.0

SECONDARY outcome

Timeframe: 1 week

Steady-state plasma concentrations of AR-42 at the time of tumor resection are provided.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
AR-42 Plasma Concentration	107.58 nanomolar (nM) Interval 3.4 to 303.7

SECONDARY outcome

Timeframe: 1 week

Concentrations of AR-42 at the tumor capsule are provided.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
AR-42 Tumor Concentration (Capsule)	325.1 nanomolar (nM) Interval 16.2 to 5296.6

SECONDARY outcome

Timeframe: 1 week

Intra-tumor concentrations of AR-42 at the tumor center are reported.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
AR-42 Tumor Concentration (Center)	645.18 nanomolar (nM) Interval 7.1 to 1766.2

SECONDARY outcome

Timeframe: 1 week

Capsule/plasma intra-tumor AR-42 concentrations are provided as a ratio.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
AR-42 Tumor Concentration (Capsule/Plasma)	13.078 ratio Interval 1.72 to 53.4

SECONDARY outcome

Timeframe: 1 week

Center/plasma intra-tumoral AR-42 concentrations are provided as a ratio.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
AR-42 Tumor Concentration (Center/Plasma)	5.748 ratio Interval 1.59 to 17.8

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 weeks

We report the average total number of doses of AR-42 taken per participant during this study.

Outcome measures

Outcome measures
Measure	AR-42 Administration n=5 Participants There was no randomization in this trial and all participants completed study procedures uniformly. AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, which was 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. All participants were instructed to take the study medication at least 1 hour before, or 2 hours after, a meal. The principal investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Number of Doses of AR-42 Received	9 total doses Interval 8.0 to 11.0

Adverse Events

AR-42 Administration

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	AR-42 Administration n=5 participants at risk AR-42 was administered three times per week beginning 3 weeks prior to surgery. AR-42 was administered in a total of ten oral doses, +/- 1 dose, at 40 mg/dose, and was 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. A study investigator performed the clinically indicated surgical procedure 3 weeks post-initial dose of medication as well as the specimen collection.
Blood and lymphatic system disorders Thrombocytopenia	60.0% 3/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
General disorders Fatigue	60.0% 3/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
General disorders Nausea	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Gastrointestinal disorders Diarrhea	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Blood and lymphatic system disorders Anemia	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Blood and lymphatic system disorders Leukopenia	60.0% 3/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Blood and lymphatic system disorders Neutropenia	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Psychiatric disorders Confusion	80.0% 4/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Blood and lymphatic system disorders Lymphopenia	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Musculoskeletal and connective tissue disorders Myalgia	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Nervous system disorders Taste change	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
General disorders Headache	60.0% 3/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Gastrointestinal disorders Dyspepsia	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Nervous system disorders Facial weakness	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Skin and subcutaneous tissue disorders Rash	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Blood and lymphatic system disorders Leukocytosis	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
General disorders Non-cardiac chest pain	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Nervous system disorders CSF leak	40.0% 2/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Nervous system disorders Tremor	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.
Eye disorders Scleral disorder	20.0% 1/5 • Participants were observed for adverse events over 5 weeks, beginning 3 weeks prior to surgery and ending 2 weeks after surgery. This interval included perioperative adverse events and surgical complications associated with AR-42. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and were also recorded according to severity, expectedness, and relatedness to the investigational treatment. Participants were encouraged throughout the study to spontaneously report all adverse events promptly to their physician-investigator.

Additional Information

Matthew E Stenerson, MSc, Clinical Research Project Manager

Mass General Brigham

Phone: 7155721100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place