Trial Outcomes & Findings for Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas (NCT NCT02129647)

NCT ID: NCT02129647

Last Updated: 2021-12-01

Results Overview

The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 13 participants
• Primary outcome timeframe: 10 days
• Results posted on: 2021-12-01

Participant Flow

Participant milestones

Measure	Axitinib 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Overall Study STARTED	13
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Axitinib 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Overall Study Adverse Event	2
Overall Study surgical intervention for clinically progressive disease	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Axitinib n=13 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Age, Continuous	39 years n=13 Participants
Sex: Female, Male Female	9 Participants n=13 Participants
Sex: Female, Male Male	4 Participants n=13 Participants
Region of Enrollment United States	13 participants n=13 Participants

PRIMARY outcome

Timeframe: 10 days

The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).

Outcome measures

Measure	Axitinib n=10 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Expression Levels of p-S6 Based Immunohistochemistry (Histoscore)	90 score Interval 0.0 to 220.0

PRIMARY outcome

Timeframe: 10 days

The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).

Outcome measures

Measure	Axitinib n=10 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Expression Levels of p-ERK Based Immunohistochemistry (Histoscore)	180 score Interval 40.0 to 220.0

PRIMARY outcome

Timeframe: 10 days

The histoscore is given as the sum of the percentage of staining multiplied by an ordinal value corresponding to the intensity level (0 = none, 1 = weak, 2 = moderate, 3 = strong). With 4 intensity levels, the resulting score ranged from 0 (no staining in the tumor) to 300 (diffuse intense staining of the tumor).

Outcome measures

Measure	Axitinib n=10 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Expression Levels of p-AKT Based Immunohistochemistry (Histoscore)	42 score Interval 5.0 to 100.0

PRIMARY outcome

Timeframe: Baseline

Population: No controls - Given that only a single surgery is generally performed to resect meningiomas and schwannomas without prior biopsy, obtaining matched control of pre and post treatment samples from the same tumor was not feasible. The study team therefore relied on matched archival control tissue for comparisons of other outcome measures; Everolimus blood levels not being one of them.

Outcome measures

Measure	Axitinib n=10 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Pre-Operative Everolimus Blood Levels	17.4 ng/ml Interval 6.9 to 49.6

PRIMARY outcome

Timeframe: 10 days

Population: No controls - Given that only a single surgery is generally performed to resect meningiomas and schwannomas without prior biopsy, obtaining matched control of pre and post treatment samples from the same tumor was not feasible. The study team therefore relied on matched archival control tissue for comparisons of other outcome measures; Everolimus blood levels not being one of them.

Outcome measures

Measure	Axitinib n=10 Participants 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Post-Operative Everolimus Blood Levels	9.4 ng/ml Interval 6.3 to 43.4

Adverse Events

Axitinib

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Axitinib n=10 participants at risk 5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Gastrointestinal disorders Mucositis	30.0% 3/10 • Number of events 3 • 10 days
General disorders nausea	10.0% 1/10 • Number of events 1 • 10 days
General disorders Fatigue	10.0% 1/10 • Number of events 1 • 10 days
Skin and subcutaneous tissue disorders Rash	10.0% 1/10 • Number of events 1 • 10 days

Additional Information

Theodore Nicolaides

NYU Langone

Phone: 212-263-9959

Email: Theodore.Nicolaides@nyualangone.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place