A Phase I Study of the Combination of Radiation Therapy (RT), Arsenic Trioxide (ATO) and Temozolomide (TMZ) in Patients With Newly-Diagnosed Glioblastoma Multiforme (GBM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose of arsenic trioxide
研究概览
简要总结
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as arsenic trioxide and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Arsenic trioxide and temozolomide may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with temozolomide and radiation therapy in treating patients with newly diagnosed high-grade glioma.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of arsenic trioxide when administered sequentially with temozolomide during radiotherapy in patients with newly diagnosed glioblastoma multiforme.
- Determine the dose-limiting toxicities of this regimen in these patients.
OUTLINE: This is a dose-escalation study of arsenic trioxide.
Patients undergo radiotherapy (may be intensity-modulated) on days 1-5. Patients also receive arsenic trioxide IV over 1-2 hours on days 1-5, and oral temozolomide on days 1-7. Treatment with radiotherapy, arsenic trioxide, and temozolomide repeats every week for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may then receive oral temozolomide on days 1-5. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Newly diagnosed grade III or IV glioma including any of the following:
- •Glioblastoma
- •Anaplastic astrocytoma
- •Gliosarcoma
- •Anaplastic oligodendroglioma
- •Anaplastic oligoastrocytoma
- •Measurable or nonmeasurable disease
- •No more than 5 weeks since prior brain surgery
- •Recovered from surgery, post- operative infection, and other complications
- •Preoperatively and postoperatively diagnostic contrast-enhanced MRI or CT scan of the brain performed prior to radiation therapy
- •Patients diagnosed by stereotactic biopsy do not require the postoperative scan
- •PATIENT CHARACTERISTICS:
- •Karnofsky performance status ≥ 60%
- •Absolute neutrophil count ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
- •Total bilirubin ≤ 2.0 mg/dL
- •AST ≤ 4.0 times ULN
- •No prolonged QT interval > 460 milliseconds on baseline electrocardiogram in the presence of normal serum potassium and magnesium
- •No uncontrolled electrolyte imbalance (i.e., sodium < 132 mmol/L, potassium < 3.5 mEq/dL, magnesium < 1.7 mg/dL)
- •No history of torsades de pointes type of ventricular arrhythmia
- •Negative pregnancy test
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No medical or psychiatric illness that, in the investigator's opinion, could potentially preclude the completion of study therapy
- •No HIV positivity
- •No active connective tissue disorders (e.g., lupus or scleroderma) that, in the investigator's opinion, may put the patient at high risk for radiation toxicity
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No prior brain radiotherapy or chemotherapy for brain tumor
- •Concurrent corticosteroids to control cerebral edema allowed provided dose is stable or decreasing for the past 5 days
- •No concurrent or plan to receive drugs that are known to prolong the QT interval
- •No prior radiation to the head or neck (except for T1 glottic cancer) resulting in overlap of radiation fields
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose of arsenic trioxide
Dose-limiting toxicities as measured by CTCAE version 3.0
次要结局
未报告次要终点