NCT01632228已完成2 期
A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study Evaluating the Efficacy and Safety of Onartuzumab in Combination With Bevacizumab or Onartuzumab Monotherapy in Patients With Recurrent Glioblastoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 62
- 主要终点
- Progression-free survival (PFS) as Assessed by Investigator According to Response Assessment in Neuro-Oncology (RANO) Criteria
研究概览
简要总结
This randomized, double-blind, placebo-controlled, multicenter phase II study will evaluate the safety and efficacy of onartuzumab in combination with bevacizumab as compared to bevacizumab alone in participants with recurrent glioblastoma. Participants will be randomized 1:1 to receive either placebo plus bevacizumab every 3 weeks, or onartuzumab plus bevacizumab. Study treatment will continue until disease progression, unacceptable toxicity, participants or physician decision to discontinue, or death.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed glioblastoma at first recurrence after concurrent or adjuvant chemoradiotherapy
- •Imaging confirmation of first tumor progression or regrowth as defined by RANO criteria
- •Prior treatment with temozolomide
- •No more than one prior line of chemotherapy
- •No prior treatment with bevacizumab or other vascular endothelial growth factor (VEGF)- or VEGF-receptor-targeted agent
- •No prior exposure to experimental treatment targeting either hepatocyte growth factor (HGF) or Met pathway
- •No prior treatment with prolifeprospan 20 with carmustine wafer
- •No prior intracerebral agent
- •Recovery from the toxic effects of prior therapy
- •No evidence of recent hemorrhage on baseline magnetic resonance imaging (MRI) of the brain
- •No need for urgent palliative intervention for primary disease (e.g. impending herniation)
- •Karnofsky performance status greater than or equal to (>=) 70 percent (%)
- •Stable or decreasing dose of corticosteroids within 5 days prior to randomization
- •Prior therapy with gamma knife or other focal high-dose radiotherapy is allowed, but the participant must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
- •Participants who have undergone recent surgery for recurrent or progressive tumor are eligible provided that: surgery must have confirmed the recurrence, a minimum of 28 days must have elapsed from the day of surgery to randomization and for core or needle biopsy, a minimum of 7 days must have elapsed prior to randomization, and craniotomy or intracranial biopsy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of randomization
- •Availability of formalin fixed paraffin embedded tumor tissue representative of glioblastoma
排除标准
- •Pregnant or lactating women
- •Inadequate hematologic, renal or liver function
- •History or presence of serious cardio-vascular disease
- •New York Heart Association Grade II or greater congestive heart failure
- •History of another malignancy in the previous 3 years, except for in situ cancer or basal or squamous cell skin cancer
- •Inadequately controlled hypertension (defined as systolic blood pressure greater than [>]150 millimeter of mercury (mmHg) and/or diastolic blood pressure >100 mmHg while on antihypertensive medication)
- •Prior history of hypertensive crisis or hypertensive encephalopathy
- •Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization
- •Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- •Known hypersensitivity to any excipients of onartuzumab or bevacizumab
研究组 & 干预措施
Onartuzumab + Bevacizumab
Experimental
All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.
干预措施: Bevacizumab (Drug)
Onartuzumab + Bevacizumab
Experimental
All participants will receive onartuzumab intravenous (IV) infusion followed by bevacizumab IV infusion every 3 weeks.
干预措施: Onartuzumab (Drug)
Placebo + Bevacizumab
Active Comparator
All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
干预措施: Bevacizumab (Drug)
Placebo + Bevacizumab
Active Comparator
All participants will receive placebo matched with onartuzumab followed by bevacizumab IV infusion every 3 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free survival (PFS) as Assessed by Investigator According to Response Assessment in Neuro-Oncology (RANO) Criteria
时间窗: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
Progression-free survival (PFS) as Assessed by Investigator According to RANO Criteria (in Participants With Met-Positive Glioblastoma)
时间窗: Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months)
次要结局
- Overall Survival (All Participants)(Baseline until death (up to approximately 18 months))
- Percentage of Participants who Survived at Month 9 (All Participants)(Month 9)
- Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (All Participants)(Month 6)
- Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (All Participants)(Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months))
- Duration of Response, as Assessed by RANO Criteria(Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months))
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to approximately 3 years 8 months)
- Minimum Observed Serum Concentration (Cmin) of Onartuzumab(predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Onartuzumab 60 minutes))
- Percentage of Participants With Serum Anti-Therapeutic Antibody (ATAs) to Onartuzumab(Predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years; Cycle length: 21 days))
- Overall Survival (in Participants With Met-Positive Glioblastoma)(Baseline until death (up to approximately 18 months))
- Percentage of Participants who Survived at Month 9 (in Participants With Met-Positive Glioblastoma)(Month 9)
- Percentage of Participants who are Progression Free at Month 6, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)(Month 6)
- Percentage of Participants With Objective Response (OR), as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)(Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months))
- Duration of Response, as Assessed by RANO Criteria (in Participants With Met-Positive Glioblastoma)(Baseline until disease progression, intolerable toxicity, participant or physician decision, or death, whichever occurs first (assessed every 6 weeks up to 18 months))
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) in Participants With Met-Positive Glioblastoma(Baseline up to approximately 3 years 8 months)
- Maximum Observed Serum Concentration (Cmax) of Onartuzumab(predose (0 hour) and 30 minutes post dose on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Onartuzumab 60 minutes))
- Minimum Observed Serum Concentration (Cmin) of Bevacizumab(predose (0 hour) on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Bevacizumab 90 minutes))
- Maximum Observed Serum Concentration (Cmax) of Bevacizumab(predose (0 hour) and 30 minutes post dose on Day 1 of Cycles 1, 2, 3, 4, at study completion or study drug discontinuation visit (up to approximately 3.5 years) (Cycle length: 21 days; infusion duration: Bevacizumab 90 minutes))
研究者
研究点 (62)
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