A Phase III Trial Comparing Whole Brain Radiation and Stereotactic Radiosurgery Alone Versus With Temozolomide or Erlotinib in Patients With Non-Small Cell Lung Cancer and 1-3 Brain Metastases
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 126
- 试验地点
- 83
- 主要终点
- Overall Survival
研究概览
简要总结
This randomized phase III trial is studying whole-brain radiation therapy and stereotactic radiosurgery with or without temozolomide or erlotinib to see how well they work compared to whole-brain radiation therapy and stereotactic radiosurgery in treating patients with brain metastases secondary to non-small cell lung cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Stereotactic radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by blocking blood flow to the tumor. It is not yet known whether radiation therapy and stereotactic radiosurgery are more effective with or without temozolomide or erlotinib in treating brain metastases.
详细描述
PRIMARY OBJECTIVES:
I. Compare survival in patients with non-small cell lung cancer and brain metastases treated with whole brain radiotherapy and stereotactic radiosurgery with vs without temozolomide or erlotinib.
SECONDARY OBJECTIVES:
I. Compare time to CNS progression in patients treated with these regimens. II. Compare quality-adjusted survival in patients treated with these regimens. III. Compare 3-month quality of life in patients treated with these regimens. IV. Compare the 6-month performance status of patients treated with these regimens.
V. Compare 6-month steroid dependence in patients treated with these regimens. VI. Compare cause of death (neurologic vs other) in patients treated with these regimens.
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 non-small cell lung cancer
- •One to 3 intraparenchymal brain metastases by contrast-enhanced MRI, meeting the following criteria:
- •Well circumscribed tumor(s)
- •Maximum diameter ≤ 4.0 cm
- •If multiple lesions are present and one lesion is at the maximum diameter, the other lesions must not exceed 3.0 cm in maximum diameter
- •No metastases within 10 mm of the optic apparatus such that a portion of the optic nerve or chiasm would be included in the high-dose stereotactic radiosurgery boost field
- •No metastases in the brainstem, midbrain, pons, or medulla
- •No prior complete resection of all known brain metastases
- •Subtotal resection allowed provided residual disease is ≤ 4.0 cm in maximum diameter
- •No clinical or radiographic evidence of progression (other than study lesion[s]) within the past month
- •Patients with brain metastases at initial presentation do not require 1 month of scans documenting stable disease
- •Stable extracranial metastases allowed
- •No known or pre-existing liver metastases
- •No leptomeningeal metastases by MRI or cerebrospinal fluid evaluation
- •Synchronous brain metastases at initial diagnosis allowed
- •Performance status - Zubrod 0-1
- •Hemoglobin ≥ 8 g/dL
- •Absolute neutrophil count ≥ 1,000/mm^3
- •Platelet count ≥ 100,000/mm^3
- •AST < 2 times upper limit of normal (ULN)
- •Alkaline phosphatase < 2 times ULN unless due to elevated bone metastases
- •Total bilirubin normal
- •Lactic dehydrogenase < 2 times ULN
- •Creatinine < 1.5 times ULN
- •No clinically active interstitial lung disease
- •Chronic stable asymptomatic radiographic changes allowed
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •HIV negative
- •Neurologic function status 0-2
- •No other major medical illness or psychiatric impairment that would preclude study participation
- •No history of allergic reaction attributed to compounds of similar chemical or biologic composition to erlotinib or temozolomide
- •No concurrent immunotherapy
- •No concurrent biologic therapy, excluding growth factors and epoetin alfa
- •No prior temozolomide or erlotinib
- •No other concurrent chemotherapy during study radiotherapy
- •Other concurrent chemotherapy allowed after study radiotherapy, except for the following:
- •Temozolomide or erlotinib (arm I only)
- •Erlotinib (arm II only)
- •Temozolomide (arm III only)
- •No prior cranial radiotherapy
- •No concurrent intensity-modulated radiotherapy
- •Concurrent radiotherapy to painful bone lesions allowed
- •No concurrent radiotherapy to more than 15% of bone marrow
- •No other concurrent therapy for brain metastases unless a recurrence is detected
- •More than 30 days since prior investigational drugs
- •No concurrent enzyme-inducing antiepileptic drugs including, but not limited to, any of the following (for patients randomized to receive erlotinib):
- •Phenytoin
- •Carbamazepine
- 另有 6 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm I
Patients undergo whole brain radiotherapy (WBRT) once daily on days 1-5, 8-12, and 15-19. Within 14 days after completion of WBRT, patients undergo stereotactic radiosurgery.
干预措施: Stereotactic Radiosurgery (Radiation)
Arm II
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm II
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Stereotactic Radiosurgery (Radiation)
Arm II
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral temozolomide once daily on days 1-21. Beginning 4 weeks after completion of WBRT, patients may receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Temozolomide (Drug)
Arm III
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
干预措施: 3-Dimensional Conformal Radiation Therapy (Radiation)
Arm III
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
干预措施: Erlotinib Hydrochloride (Drug)
Arm III
Patients undergo WBRT and stereotactic radiosurgery as in arm I. Beginning on the first day of WBRT, patients receive oral erlotinib once daily for up to 6 months.
干预措施: Stereotactic Radiosurgery (Radiation)
结局指标
主要结局
Overall Survival
时间窗: From randomization to date of death or last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.
Survival time is defined as time from randomization to date of death from any cause and estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact.
次要结局
- Change in Functional Assessment of Cancer Therapy-Brain (FACT-Br) Score at 3 Months(From randomization to three months.)
- Change in Steroid Dependence at Six Months(From randomization to six months.)
- Cause of Death (Neurologic vs Other)(From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.)
- Rate of CNS Progression (One Year)(From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.)
- Quality-adjusted Survival as Measured by EuroQol 5-dimension Instrument(From randomization to last follow-up, up to 48.1 months. Analysis occurs after all patients have been potentially followed for 9 months.)
- Change in Performance Status at Six Months(From randomization to six months.)