Trial Outcomes & Findings for Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas (NCT NCT01767792)

NCT ID: NCT01767792

Last Updated: 2021-02-12

Results Overview

Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2021-02-12

Participant Flow

Participant milestones

Measure	Bevacizumab Safety and tolerability of bevacizumab for 2 years. Change in hearing response will also be monitored.
Overall Study STARTED	22
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas

Baseline characteristics by cohort

Measure	Bevacizumab n=22 Participants Follow participant for 2 years and assess hearing response rates Bevacizumab: Treatment will be administered on an outpatient basis. Bevacizumab is administered by IV infusion at a dose of 10 mg/kg every 2 weeks for 24 weeks (induction therapy, see Schema). One cycle lasts 28 days and includes two infusions of bevacizumab. Clinical response will be assessed by audiology and MRI at weeks 12 and 24. Subjects with hearing decline at weeks 12 and 24 will be taken off of protocol. After week 24, patients with a clinical response or stable disease (together comprising "clinical benefit") will transition to maintenance therapy with bevacizumab. During the maintenance phase, subjects will be treated with open-label bevacizumab 5 mg/kg every 3 weeks for up to 72 weeks. Subjects will be followed with audiology and MRI scans every 12 weeks. The total time of the study will be 96 weeks (24 weeks induction + 72 weeks maintenance).
Age, Continuous	29 years STANDARD_DEVIATION 14.6 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 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	2 Participants n=5 Participants
Race (NIH/OMB) White	20 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	22 participants n=5 Participants
Word recognition score in target ear	53 number correct words n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: All participants treated with bevacizumab.

Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.

Outcome measures

Measure	Bevacizumab n=22 Participants Induction (high dose) therapy.
Improvement in Hearing	9 Participants

SECONDARY outcome

Timeframe: 6 months

Population: All participants treated with bevacizumab.

Number of participants with adverse events occurring in at least 10% of participants during induction therapy.

Outcome measures

Measure	Bevacizumab n=22 Participants Induction (high dose) therapy.
Number of Participants With Adverse Events	22 Participants

SECONDARY outcome

Timeframe: 6 months

Population: All participants treated with bevacizumab.

Number of participants who did not stop treatment due to side effects or by participant/provider choice during induction period.

Outcome measures

Measure	Bevacizumab n=22 Participants Induction (high dose) therapy.
Tolerability of Bevacizumab During Induction (High Dose) Therapy	21 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Analysis population is restricted to participants who achieved hearing improvement during induction (high dose) therapy.

Number of participants with hearing improvement during induction therapy who maintained hearing improvement relative to baseline during maintenance therapy as measured by word recognition score.

Outcome measures

Measure	Bevacizumab n=7 Participants Induction (high dose) therapy.
Durability of Hearing Response During Maintenance (Low Dose) Therapy	4 Participants

SECONDARY outcome

Timeframe: Weeks 25, 49, 73, 98

Population: All participants treated during maintenance (low dose) therapy.

Increase in pure tone average represents worsening of hearing and decrease in pure tone average represents improvement of hearing. Range for for pure tone average (PTA) is 0-110 dBHL (decibels).

Outcome measures

Measure	Bevacizumab n=20 Participants Induction (high dose) therapy.
Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL). Change from week 25 to week 49	-1.19 decibels (dBHL) Standard Error 1.91
Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL). Change from week 25 to week 73	1.05 decibels (dBHL) Standard Error 1.91
Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL). Change from week 25 to week 98	-0.95 decibels (dBHL) Standard Error 2.09

SECONDARY outcome

Timeframe: 6 months (induction phase)

Population: Number of participants with data at baseline and month 6.

Self-reported distress measured using the tinnitus reaction questionnaire (TRQ). TRQ has 26 questions measured on a 5-point Likert scale from 0 (not at all) to 4 (almost all of the time). The total score is the sum of the responses with higher scores indicating more reported distress.

Outcome measures

Measure	Bevacizumab n=21 Participants Induction (high dose) therapy.
Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.	14.3 units on a scale Standard Deviation 18.2

SECONDARY outcome

Timeframe: 2 years

Population: Analysis population is restricted to participants who achieved hearing improvement during induction (high dose) therapy.

Count of participants who achieved a 20% or more reduction in tumor volume over baseline during induction (high dose) therapy and maintained this decrease during maintenance (low dose) therapy (decline in tumor volume from baseline of 20% or more).

Outcome measures

Measure	Bevacizumab n=7 Participants Induction (high dose) therapy.
Durability of Radiographic Response	5 Participants

Adverse Events

Bevacizumab

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Bevacizumab n=22 participants at risk Safety and tolerability of bevacizumab for 2 years. Change in hearing response will also be monitored.
Nervous system disorders Headache	4.5% 1/22 • Number of events 1 • Adverse event data collected for 2 years

Other adverse events

Measure	Bevacizumab n=22 participants at risk Safety and tolerability of bevacizumab for 2 years. Change in hearing response will also be monitored.
Vascular disorders Hypertension	50.0% 11/22 • Number of events 28 • Adverse event data collected for 2 years
Nervous system disorders Fatigue	36.4% 8/22 • Number of events 17 • Adverse event data collected for 2 years
Nervous system disorders Headache	31.8% 7/22 • Number of events 13 • Adverse event data collected for 2 years
Reproductive system and breast disorders Irregular menstruation	27.3% 6/22 • Number of events 9 • Adverse event data collected for 2 years
Respiratory, thoracic and mediastinal disorders Epistaxis	22.7% 5/22 • Number of events 8 • Adverse event data collected for 2 years
Gastrointestinal disorders Diarrhea	18.2% 4/22 • Number of events 6 • Adverse event data collected for 2 years
Gastrointestinal disorders Nausea	18.2% 4/22 • Number of events 5 • Adverse event data collected for 2 years
Renal and urinary disorders Proteinuria	18.2% 4/22 • Number of events 5 • Adverse event data collected for 2 years
Gastrointestinal disorders Abdominal pain	13.6% 3/22 • Number of events 3 • Adverse event data collected for 2 years
Musculoskeletal and connective tissue disorders Arthralgia	13.6% 3/22 • Number of events 4 • Adverse event data collected for 2 years
Investigations AST increased	13.6% 3/22 • Number of events 3 • Adverse event data collected for 2 years
Musculoskeletal and connective tissue disorders Back pain	13.6% 3/22 • Number of events 3 • Adverse event data collected for 2 years
Metabolism and nutrition disorders Hyperglycemia	13.6% 3/22 • Number of events 3 • Adverse event data collected for 2 years
Gastrointestinal disorders Mucositis oral	13.6% 3/22 • Number of events 11 • Adverse event data collected for 2 years

Additional Information

Bruce Korf, MD, PhD

The University of Alabama at Birmingham

Phone: 205.934.4010

Email: bkorf@uabmc.edu

Results disclosure agreements

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

Restriction type: GT60