A Pilot and Phase II Study of OSI-774 and Temozolomide in Combination With Radiation Therapy in Glioblastoma Multiforme
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 171
- 试验地点
- 139
- 主要终点
- Survival
研究概览
简要总结
This pilot phase II trial is studying the side effects and best dose of erlotinib when given with temozolomide and radiation therapy and to see how well they work in treating patients with glioblastoma multiforme or other brain tumors. Radiation therapy uses high-energy x-rays to damage tumor cells. Erlotinib may interfere with the growth of tumor cells, slow the growth of the tumor, and make the tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining erlotinib and temozolomide with radiation therapy may kill more tumor cells.
详细描述
PILOT STUDY OBJECTIVES:
I. Determine the maximum tolerated dose of erlotinib administered with temozolomide and radiotherapy in patients with glioblastoma multiforme or other grade 4 brain tumors who are currently on enzyme-inducing anticonvulsant (EIAC) therapy vs no EIAC therapy.
II. Determine the safety and tolerability of this regimen in these patients. III. Determine the toxic effects of this regimen in these patients. IV. Determine the efficacy of this regimen, in terms of 1-year survival, in these patients.
PHASE II OBJECTIVES:
I. Determine the response rate and time to progression in patients treated with this regimen.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of 1 of the following:
- •Glioblastoma multiforme (grade 4 astrocytoma)
- •Gliosarcomas
- •Other grade 4 astrocytoma variants (e.g., giant cell)
- •Must be enrolled at least 1 week, but no more than 4 weeks, after prior biopsy or surgery
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •At least 6 months
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Hemoglobin ≥ 9 g/dL
- •Total bilirubin ≤ upper limit of normal (ULN)
- •AST no greater than 2.5 times ULN
- •Creatinine no greater than 1.5 times ULN
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No inability to take oral medications
- •No requirement for IV alimentation
- •No active uncontrolled peptic ulcer disease
- •No abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
- •No congenital abnormality (e.g., Fuch's dystrophy)
- •No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
- •No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)
- •No prior allergy or intolerance to dacarbazine
- •No other active malignancy requiring treatment
- •No other concurrent uncontrolled illness
- •No ongoing or active infection
- •No psychiatric illness or social situation that would preclude study compliance
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior chemotherapy for any brain tumor
- •No prior temozolomide
- •No prior radiotherapy for any brain tumor
- •No other concurrent investigational agents
- •More than 21 days since prior major surgery (excluding neurosurgical biopsy or brain tumor resection)
- •No prior surgical procedures affecting absorption
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No concurrent warfarin
排除标准
- 未提供
研究组 & 干预措施
Treatment (erlotinib hydrochloride, radiation, temozolomide)
Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: erlotinib hydrochloride (Drug)
Treatment (erlotinib hydrochloride, radiation, temozolomide)
Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: 3-dimensional conformal radiation therapy (Radiation)
Treatment (erlotinib hydrochloride, radiation, temozolomide)
Patients receive oral erlotinib once daily. After 1 week of erlotinib alone, patients also receive oral temozolomide once daily for 6 weeks and undergo concurrent radiotherapy 5 days a week for 6 weeks. After completion of radiotherapy, patients continue to receive erlotinib once daily alone in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of radiotherapy, patients also receive oral temozolomide once daily for 5 days. Temozolomide treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temozolomide (Drug)
结局指标
主要结局
Survival
时间窗: At 52 weeks
Overall survival distribution
时间窗: From start of study therapy to death due to any cause, up to 15 years
The overall survival distribution will be estimated using the method of Kaplan-Meier. The success probability, i.e., 12-month survival percentage, will be estimated as the number of evaluable patients still alive at 366 days divided by the total number of evaluable patients followed for at least 366 days.
次要结局
- Time-to-disease progression(From start of study therapy to documentation of disease progression, up to 15 years)
- Maximum toxicity grade, assessed by Common Terminology Criteria for Adverse Events (CTCAE)(Up to 15 years)