Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Six-month Progression-free Survival (PFS6)
研究概览
简要总结
It has been shown that bevacizumab has significant anti-tumor activity in patients with recurrent glioblastoma multiforme. Vorinostat has modest anti-tumor activity against malignant glioma and can enhance the action of both chemotherapy and anti-angiogenics. Patients will be treated with a combination of bevacizumab and vorinostat.
详细描述
There is no effective therapy for patients with recurrent glioblastoma multiforme (GBM) hence such patients remain a major unmet need in oncology. The investigators have recently demonstrated that bevacizumab (BV), a humanized monoclonal antibody against vascular endothelial growth factor, has significant anti-tumor activity among recurrent glioblastoma multiforme patients. Vorinostat has modest anti-tumor activity against malignant glioma and can potentiate the action of both chemotherapy and anti-angiogenics. The current study is designed to evaluate the anti-tumor activity of vorinostat when combined with BV among recurrent glioblastoma multiforme patients.
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
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years.
- •An interval of at least 4 weeks between prior surgical resection or one week from stereotactic biopsy.
- •An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there is biopsy-proven tumor progression
- •An interval of at least 4 weeks from prior chemotherapy [6 weeks for nitrosoureas, 1 week for daily administered chemotherapy (metronomic dosing)] or investigational agent unless the patient has recovered from all anticipated toxicities associated with that therapy.
- •Eastern Cooperative Oncology Group (ECOG) 0-
- •Hematocrit ≥ 29%, hemoglobin ≥ 9, absolute neutrophil ≥1,500 cells/microliter, platelets ≥ 100,000 cells/microliters.
- •Serum creatinine, serum glutamic oxaloacetic transaminase(SGOT) and bilirubin < 1.5 times upper limit of normal.
- •Signed informed consent approved by the Institutional Review Board prior to patient entry.
- •No evidence of hemorrhage on the baseline MRI or CT scan other than those that are stable grade
- •If sexually active, patients will take contraceptive measures for the duration of the treatments. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation, hysterectomy, vasectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD).
排除标准
- •Disease-specific exclusions
- •More than 2 prior episodes of disease progression
- •Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and patients previously treated with valproic acid must be off valproic acid for at least 30 days prior to initiation of study medication
- •Prior bevacizumab therapy
- •Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
- •Active infection requiring intravenous antibiotics
- •Severe hepatic insufficiency, active viral hepatitis or HIV infection
- •Requires therapeutic anti-coagulation with warfarin
- •General medical exclusions
- •Subjects meeting the following criteria are ineligible for study entry:
- •Inability to comply with study and/or follow-up procedures
- •Bevacizumab-specific exclusions
- •Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- •Any prior history of hypertensive crisis or hypertensive encephalopathy
- •New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
- •History of myocardial infarction or unstable angina within 6 months prior to study enrollment
- •History of stroke or transient ischemic attack within 6 months prior to study enrollment
- •Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- •Symptomatic peripheral vascular disease
- •Evidence of bleeding diathesis or coagulopathy
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- •Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- •Serious, non-healing wound, ulcer, or bone fracture
- •Proteinuria at screening as demonstrated by either:
- •Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR
- •Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- •Known hypersensitivity to any component of bevacizumab
- •Pregnant (positive pregnancy test) or lactating. Refuse the use of effective means of contraception (men and women) in subjects of child-bearing potential
研究组 & 干预措施
Vorinostat & Bevacizumab
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
干预措施: Bevacizumab (Drug)
Vorinostat & Bevacizumab
Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.
干预措施: Vorinostat (Drug)
结局指标
主要结局
Six-month Progression-free Survival (PFS6)
时间窗: 6 months
The percentage of participants alive and progression-free at 6 months after the start of study treatment will be determined. Based on Response Assessment in Neuro-Oncology (RANO) criteria, progression is defined as a ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions; significant increase in T2/FLAIR; any new lesion; clear clinical deterioration not attributable to other causes apart from the tumor; failure to return for evaluation as a result of death or deteriorating condition; or clear progression of non-measurable disease. PFS6 will be calculated from the date study treatment started until the date of progression or death, or the date of last follow-up if participants are alive without progression. Kaplan-Meier methods will be used to estimate survival.
次要结局
- Radiographic Response(3 Years)
- Percentage of Participants Who Experience Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.(2.7 Years)
- Median Progression-free Survival (PFS)(3 Years)
- Median Overall Survival (OS)(3 Years)