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 Treatment With Surgery or Radiation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 12
- 主要终点
- Improvement in Hearing
研究概览
简要总结
To determine the hearing response rate at 24 weeks after treatment with bevacizumab for symptomatic vestibular schwannomas (VS) in children and young adults with Neurofibromatosis Type 2 (NF 2).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
- •Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Prior radiation treatment to the target vestibular schwannoma is allowed if provided 3 years prior to participation in the clinical trial. Prior radiation treatment to non-target tumors is allowed.
- •Participants may not be receiving any other study agents.
- •Patients with nervous system tumors associated with NF2 (e.g., schwannomas, meningiomas, ependymomas, or gliomas) will not be excluded from this clinical trial unless (in the opinion of the investigator) these tumors are growing and are likely to require treatment during the clinical trial.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab.
- •Patients with known hypersensitivity of Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biologic composition to bevacizumab.
- •Inability to tolerate periodic MRI scans or gadolinium contrast.
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
- •History of arterial/myocardial disease.
- •Clinically significant cardiovascular disease, such as:
- •Inadequately controlled hypertension (HTN) (for adults: Systolic Blood Pressure (SBP) > 160 mmHg and/or Diastolic Blood Pressure (DBP) > 90 mmHg despite antihypertensive medication; for children: please refer to Appendix D for age-appropriate values indicating ≥ Grade 2)
- •History of cerebrovascular accident (CVA) within 12 months
- •Myocardial infarction or unstable angina within 12 months
- •New York heart association grade II or greater congestive heart failure
- •Serious and inadequately controlled cardiac arrhythmia
- •Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection)
- •Clinically significant peripheral vascular disease
- •Pregnant women are excluded from this study because bevacizumab is an anti-angiogenic agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with bevacizumab, breastfeeding should be discontinued if the mother is treated with bevacizumab. These potential risks may also apply to other agents used in this study.
- •HIV-positive patients or cancer survivors are eligible for this study if they fulfill all other eligibility criteria.
- •Concurrent use of anti-coagulant drugs (not including prophylactic doses), history of coagulopathy, or evidence of bleeding diathesis or coagulopathy.
- •Imaging (CT or MRI) evidence of hemorrhage deemed significant by the treating physician (> grade 1). Subjects with history of central nervous system (CNS) hemorrhage are not eligible.
- •Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be <1000 mg for patient enrollment.
- •Serious or non-healing wound, ulcer or bone fracture.
- •History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day
- •Invasive procedures defined as follows:
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 therapy
- •Brain biopsy within 28 days prior to day 1 of therapy (wounds must be fully healed from brain biopsies performed more than 28 days prior to day 1 of therapy)
- •Anticipation of need for major surgical procedures during the course of the study
- •Core biopsy within 7 days prior to D1 therapy
- •Prior treatment with bevacizumab.
研究组 & 干预措施
Bevacizumab
Follow participant for 2 years and assess hearing response rates
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Improvement in Hearing
时间窗: 6 months
Number of participants with a statistically significant increase in word recognition score on audiology compared to baseline.
次要结局
- Number of Participants With Adverse Events(6 months)
- Tolerability of Bevacizumab During Induction (High Dose) Therapy(6 months)
- Changes in Pure Tone Average (PTA) on Audiology Compared With Baseline, Measured in Decibels (dBHL).(Weeks 25, 49, 73, 98)
- Durability of Hearing Response During Maintenance (Low Dose) Therapy(2 years)
- Changes in Distress Related to Tinnitus During Induction (High Dose) Treatment.(6 months (induction phase))
- Durability of Radiographic Response(2 years)
研究者
Bruce Korf, MD
Principal Investigator
University of Alabama at Birmingham