A Double Blind Phase II Study of BAY 43-9006 in Patients With Non-Small Cell Lung Cancer Who Have Failed at Least Two Prior Chemotherapy Regimens
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 342
- 试验地点
- 141
- 主要终点
- Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
研究概览
简要总结
RATIONALE: Preclinical studies indicate that sorafenib is a potent inhibitor of Raf kinase in vitro and in vivo, with significant dose-dependent, anti-tumor activity in four different human tumor types including colon, pancreatic, lung, and ovarian. This activity was cytostatic in nature and was maintained if dosing was continued. That is, tumor growth is suspended while the drug is administered but returns to baseline rates when the agent is withdrawn. Therefore, the optimal schedule will be an uninterrupted one. To assess the activity of sorafenib in a timely manner and with a meaningful interpretation, a randomized discontinuation design was adopted in the present trial, conducted in a population who were potentially sensitive to sorafenib.
PURPOSE: This randomized phase II trial is studying sorafenib to see how well it works compared to placebo in treating patients with refractory non-small cell lung cancer.
详细描述
OBJECTIVES:
- To determine the percent of patients maintaining stable disease or objective response two months after randomization with continued sorafenib treatment, compared to patients switched to placebo.
- To determine progression-free survival, overall survival, and response rate.
OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to number of prior chemotherapy regimens (2 vs more than 2) and prior epidermal growth factor receptor inhibitor treatment (yes vs no).
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Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
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Randomization: Patients are randomized to 1 of 2 treatment arms.
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Arm I: Patients receive oral sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
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Arm II: Patients receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients who develop disease progression within 1 year after randomization cross over to arm I.
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
- Double (Participant, Investigator)
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 or cytologically confirmed advanced non-small cell lung cancer (NSCLC)
- •Disease must have progressed after at least 2 prior chemotherapy regimens for NSCLC
- •Patients must have measurable or nonmeasurable disease
- •Absolute neutrophil count at least 1,500/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •AST and ALT no greater than 3 times ULN (5 times ULN in patients with liver disease)
- •Creatinine less than 1.5 times ULN or calculated creatinine clearance greater than 50 mL/min
- •More than 3 weeks since prior chemotherapy, radiotherapy, immunotherapy or other investigational drug use
- •Recovered from all prior therapy
- •Fertile patients must use effective contraception
- •Age >= 18
- •ECOG performance status of 0-1
排除标准
- •Prior primary or metastatic brain or meningeal tumors unless clinically and radiographically stable and off therapy for at least 2 months
- •Active second malignancy
- •Clinically evident congestive heart failure, serious cardiac arrhythmias, or symptoms of coronary heart disease
- •Prior radiotherapy to the only site of measurable or evaluable disease unless there is evidence of disease progression in that site
- •Prior exposure to a ras pathway inhibitor (e.g., farnesyl transferase inhibitor)
- •Concurrent medications known to be metabolized by the liver with a narrow therapeutic index, including the following:
- •Ketoconazole
- •Itraconazole
- •Quinidine
- •Cyclosporine
- •Ritonavir
- •Grapefruit products
- •Carbamazepine
- •Phenytoin
- •Phenobarbital
- •Pregnant or nursing
- •Clinically serious active infection
- •Medical conditions, substance abuse or psychological/social situation that would preclude study participation
研究组 & 干预措施
Induction then Sorafenib
Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease.
干预措施: Sorafenib (Drug)
Induction then Placebo then Sorafenib
Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm.
干预措施: Sorafenib (Drug)
Induction then Placebo then Sorafenib
Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.
Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm.
干预措施: Placebo (Drug)
Induction, not randomized
Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.
Post-induction: Patients with responding disease or disease progression were not randomized in Step 2. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression, while patients with disease progression were removed from the study.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Number of Patients Maintaining Stable Disease or Objective Response 2 Months After Randomization
时间窗: Two months after randomization
Per RECIST Criteria (V1.0): Complete Response (CR): disappearance of all target lesions Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions Progressive Disease (PD): \>=20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of longest diameter recorded since randomization, or the appearance of new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD
次要结局
- Progression-free Survival(Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years.)
- Overall Survival(Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years)
- Best Overall Response(Assessed every 8 weeks while on treatment. After the end of treatment, assessed every 3 months for 2 years, then every 6 months for 3 years)