Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- Proportion of Successes (Patients Alive and Progression-free)
研究概览
简要总结
This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.
II. Determine the safety and toxicity of this drug in these patients.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics of this drug in these patients. II. Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.
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
- 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 grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence
- •Progressive or recurrent disease
- •Measurable or evaluable disease by MRI or CT scan
- •Performance status - ECOG 0-2
- •WBC ≥ 3,000/mm^3
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Hemoglobin ≥ 8 g/dL
- •AST ≤ 3 times upper limit of normal (ULN)
- •Bilirubin normal
- •Creatinine ≤ 1.5 times ULN
- •No myocardial infarction within the past 6 months
- •No congestive heart failure
- •No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy
- •No known HIV positivity
- •Not immunocompromised except if related to the use of corticosteroids
- •No known hypersensitivity to any of the components of the study drug
- •No uncontrolled infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- •No other malignancy
- •No other severe disease that would preclude study participation
- •Prior adjuvant chemotherapy allowed
- •More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- •More than 2 weeks since prior small molecule cell cycle inhibitor
- •Concurrent corticosteroids allowed as long as dose has been stable for ≥ 1 week
- •At least 8 weeks since prior radiotherapy
- •Must have evidence of tumor progression by MRI or CT scan after radiotherapy
- •More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless 1 of the following criteria is met:
- •There is a separate lesion by MRI outside of the prior treatment field
- •There is evidence of recurrent disease by biopsy, MRI spectroscopy, or positron-emission tomography scan
- •More than 2 weeks since prior valproic acid
排除标准
- 未提供
研究组 & 干预措施
Stratum 1 (not undergoing surgery)
Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks 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) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: conventional surgery (Procedure)
Stratum 2 (undergoing surgery)
Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: vorinostat (Drug)
Stratum 2 (undergoing surgery)
Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: conventional surgery (Procedure)
结局指标
主要结局
Proportion of Successes (Patients Alive and Progression-free)
时间窗: At 6 months
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method. Definition of progression: Bidimensionally measurable disease: \>25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
次要结局
- Survival(From study registration to date of death due to any cause or last follow-up (up to 5 years))
- Confirmed Tumor Response(Assessed up to 5 years)
- Time to Progression(From registration to disease progression (up to 5 years))