Phase II Study of Vorinostat (SAHA) in Combination With Bortezomib (PS-341) in Patients With Recurrent Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 213
- 主要终点
- Progression-free Survival at 6 Months
研究概览
简要总结
This phase II trial is studying how well giving vorinostat together with bortezomib works in treating patients with progressive, recurrent glioblastoma multiforme. Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with bortezomib may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the clinical efficacy of vorinostat (SAHA) and bortezomib, in terms of progression-free survival (PFS) at 6 months, in patients with progressive, recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
I. To determine the clinical efficacy of this regimen, in terms of overall survival, PFS at 12 months, time to progression, and objective response rate, in these patients.
II. To identify molecular predictors of response in baseline tumor specimens from these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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 multiforme
- •Gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma) allowed
- •Recurrent disease
- •Must have evidence of tumor progression by MRI or CT scan after radiotherapy or after the most recent antitumor therapy
- •Bidimensionally measurable or evaluable disease by MRI or CT scan
- •Patients receiving corticosteroids must be on a fixed dose for at least 1 week prior to baseline scan
- •ECOG performance status 0-2
- •WBC ≥ 3,000/mm³
- •ANC ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST ≤ 3 times ULN
- •Creatinine normal
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after the last dose of vorinostat
- •Willing to provide mandatory correlative laboratory tissue samples
- •Able to take oral medications
- •No uncontrolled infection
- •No known hypersensitivity to any of the components of vorinostat or bortezomib
- •No myocardial infarction or unstable angina within the past 6 months
- •No congestive heart failure requiring use of ongoing maintenance therapy or history of life-threatening ventricular arrhythmias
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •No other active malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- •No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would preclude study entry or significantly interfere with proper assessment of safety and toxicity of the prescribed study regimens
- •Not immunocompromised
- •Patients known to be HIV positive are eligible provided there is no clinical evidence of an immunocompromised state
- •No peripheral neuropathy ≥ grade 2
- •No peripheral neuropathy with pain ≥ grade 1
- •No congenital long QT syndrome
- •No prolonged OTC interval (> 450 msec)
- •No other concurrent anticancer therapy (other than hormonal therapy)
- •At least 8 weeks since prior radiotherapy
- •More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless there is a separate lesion on MRI that is not part of the prior treatment field
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- •No more than 1 prior chemotherapy regimen* for progressive/recurrent disease (stratum 1)
- •Patients in stratum 2 may have received any number of prior chemotherapy regimens* for progressive/recurrent disease
- •More than 2 weeks since prior small molecule cell cycle inhibitors
- •More than 7 days since prior valproic acid
- •More than 7 days since prior category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
- •Quinidine, procainamide, disopyramide
- •Amiodarone, sotalol, ibutilide, dofetilide
- •Erythromycin, clarithromycin
- •Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
- •Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin,lidoflazine
- •More than 4 weeks since prior bevacizumab
- •No prior treatment with vorinostat or bortezomib
- 另有 3 项未显示
排除标准
- 未提供
研究组 & 干预措施
Stratum 1 (not undergoing surgery)
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Stratum 1 (not undergoing surgery)
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Stratum 2 (undergoing surgery)
Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.
干预措施: vorinostat (Drug)
Stratum 2 (undergoing surgery)
Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.
干预措施: therapeutic conventional surgery (Procedure)
Stratum 2 (undergoing surgery)
Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.
干预措施: bortezomib (Drug)
结局指标
主要结局
Progression-free Survival at 6 Months
时间窗: At 6 months
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months. For patients with bidimensionally measurable disease (measurable disease), progression is defined as \> 25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. For patients without bidimensionally measurable disease (evaluable disease), progression is defined as unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians or appearance of new lesions.
次要结局
- Overall Survival(From study registration to date of death due to any cause or last follow-up (up to 5 years))
- Time to Progression(From study registration to date of progression (up to 5 years))
- Proportion of Confirmed Tumor Response Defined as an Objective Status of Confirmed Response (CR), Partial Response (PR), or Regression (REGR) on Two Consecutive Evaluations(Assessed up to 5 years)