A Phase II Clinical Trial of the Histone Deacetylase Inhibitor Valproic Acid in Combination With Temodar and Radiation Therapy in Patients With High Grade Gliomas: Multi-Institutional Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 3
- 主要终点
- Percentage of Participants With Overall Survival at 6, 12, and 24 Months
研究概览
简要总结
Background:
- Radiation therapy with temozolomide (an anti-cancer drug) is standard therapy for treating brain tumors called glioblastomas.
- The drug valproic acid, currently approved for treating seizures, has been shown in laboratory tests to increase the radiosensitivity of glioma cells.
Objectives:
-To determine the effectiveness of adding valproic acid to standard treatment with radiation therapy and temozolomide for treating glioblastoma.
Eligibility:
-Patients 18 years of age and older with glioblastoma multiforme who have not been previously treated with chemotherapy of radiation.
Design:
- This Phase II trial will enroll 41 patients.
- Patients will receive radiation therapy to the brain once a day, Monday through Friday, for 6 1/2 weeks.
- Patients will take temozolomide once a day by mouth, Monday through Friday, during the period of radiation treatment. Starting 4 weeks after radiation therapy, patients will take temozolomide once a day for 5 days every 28 days for a total of six cycles.
- Patients will receive valproic acid by mouth twice a day beginning 1 week prior to the first day of radiation therapy and continuing until the completion of chemotherapy and radiation therapy.
- Patients will have follow-up visits 1 month after completing therapy, then every 3 months for 2 years, and then every 6 months for 3 years. Follow-up includes a physical examination, blood tests and magnetic resonance imaging of the brain.
详细描述
BACKGROUND:
- Histone deacetylase inhibitors (HDACi) have recently been shown to enhance the radiosensitivity of glioma cells both in vitro and in vivo.
- Valproic acid has also recently been demonstrated to be a potent HDAC.
- Valproic acid has a long clinical history in patients with and without brain tumors and is known to cross the blood-brain barrier. However, the use of valproic acid in combination with temozolomide and radiotherapy for patients with high-grade gliomas has never been tested.
OBJECTIVES:
-The primary measure of efficacy will be progression free survival and overall survival.
ELIGIBILITY:
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 90 Years（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
- 未提供
研究组 & 干预措施
Valproic Acid
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
干预措施: adjuvant therapy (Procedure)
Valproic Acid
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
干预措施: Temozolomide (Drug)
Valproic Acid
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
干预措施: Valproic Acid (Drug)
Valproic Acid
Orally 25mg/kg/day twice a day concurrently with radiation therapy and temozolomide.
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
Percentage of Participants With Overall Survival at 6, 12, and 24 Months
时间窗: 6, 12, and 24 months
Percentage of participants who were alive at 6, 12, and 24 months.
Percentage of Participants With Progression Free Survival at 6, 12, and 24 Months
时间窗: 6, 12, and 24 months
Percentage of participants who were progression free by 6, 12, or 24 months. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
Number of Participants With Best Response
时间窗: up to 63.8 months
Best response recorded from the start of treatment until disease progression/recurrence. Complete response is complete resolution of all contrast enhancing tumor documented at initiation of treatment on protocol, with no appearance of new lesions. Partial response is a \>50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Minor response is a \>25%, but \<50% reduction in the contrast enhancing tumor volume documented at the initiation of treatment on protocol. Stable disease is a change in tumor size less than MR but not demonstrating progressive disease. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol. Not evaluable means the participant cannot be evaluated (e.g., quality of scan).
Median Overall Survival
时间窗: up to 63.8 months
Survival is the interval from the initiation of treatment on protocol to date of death.
Median Progression Free Survival.
时间窗: up to 51 months
Progression free survival is the interval from initiation of treatment on protocol to symptomatic or radiographic progression. Progressive disease is a \>25% increase in contrast enhancing tumor volume documented at the initiation of treatment on protocol.
次要结局
- Number of Participants With Adverse Events(6 years, 7 months and 27 days)
研究者
Kevin Camphausen, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)