Clinical Trial: Phase 2 Study of Bevacizumab in Children and Young Adults With NF 2 and Progressive Vestibular Schwannomas
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: Open-label, Phase 2 Study of Bevacizumab in Children and Young Adults With Neurofibromatosis 2 and Progressive Vestibular Schwannomas That Are Poor Candidates for Standard
Brief Summary: To determine the hearing response rate at 24 weeks after treatment with bevacizumab for symptomatic vestibular schwannomas (VS) in children and young adults with NF2.
Detailed Summary:
Subjects will be treated with open-label bevacizumab 10 mg/kg every 2 weeks for 24 weeks (induction therapy). Clinical response will be assessed by audiology and MRI at weeks 12 and 24. Subjects with hearing decline at weeks 12 or 24 will be taken off of protocol. At 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).
Subjects will be allowed to increase their bevacizumab dose to 10 mg/kg every 2 weeks during maintenance therapy if they experience hearing decline during maintenance therapy (defined as decrease in word recognition score below the 95% critical difference compared with the word recognition score at baseline, Appendix A). Subjects will be taken off of study if their word recognition score does not remain within the 95% critical difference after receiving bevacizumab 10 mg/kg every 2 weeks.
Sponsor: University of Alabama at Birmingham
Current Primary Outcome: Hearing Response Rates [ Time Frame: 2 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- safety [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score; (4) to determine the durability of radiographic response, as measured from the time of first response to tumor progression (defined as an increase in volume of > 20% compared to lowest tumor volume during treatment) (5) to determine changes in function of the auditory system during bevacizumab treatment; (6) to explore changes in tinnitus during treatment.
- tolerability [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score;(4) to determine the durability of radiographic response, as measured from the time of first response to tumor progression (defined as an increase in volume of > 20% compared to lowest tumor volume during treatment) (5) to determine changes in function of the auditory system during bevacizumab treatment; (6) to explore changes in tinnitus during treatment.
- durability [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score; (4) to determine the durability of radiographic response, as measured from the time of first response to tumor progression (defined as an increase in volume of > 20% compared to lowest tumor volume during treatment) (5) to determine changes in function of the auditory system during bevacizumab treatment; (6) to explore changes in tinnitus during treatment.
- Radiographic Response [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score; (4) to determine the durability of radiographic response, as measured from the time of first response to tumor progression (defined as an increase in volume of > 20% compared to lowest tumor volume during treatment) (5) to determine changes in function of the auditory system during bevacizumab treatment; (6) to explore changes in tinnitus during treatment.
- Changes in function of auditory system [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score; (4) to determine the durability of radiographic response, as measured from the time of first response to tumor progression (defined as an increase in volume of > 20% compared to lowest tumor volume during treatment) (5) to determine changes in function of the auditory system during bevacizumab treatment; (6) to explore changes in tinnitus during treatment.
- Changes in Tinnitus during treatment [ Time Frame: 2 years ]The secondary objectives are: (1) to determine the safety and tolerability of bevacizumab in this patient population; (2) to determine the radiographic response rate (defined as an decrease in VS volume by ≥ 20% compared to baseline) during bevacizumab treatment; (3) to determine the durability of hearing response, as measured by freedom from hearing loss from the time of hearing response (defined as a decrease in word recognition score below the upper limit of the 95% critical difference of the baseline word recognition score; (4) to determine the
Original Secondary Outcome: Same as current
Information By: University of Alabama at Birmingham
Dates:
Date Received: January 7, 2013
Date Started: May 2013
Date Completion: December 2019
Last Updated: May 3, 2017
Last Verified: May 2017
