Randomized Study of Erlotinib Vs Observation in Patients With Completely Resected Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 390
- 试验地点
- 2,142
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase III ALCHEMIST trial studies how well erlotinib hydrochloride compared to observation works in treating patients with stage IB-IIIA non-small cell lung cancer that has been completely removed by surgery (resected). Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVE:
I. To assess whether adjuvant therapy with erlotinib hydrochloride (erlotinib) will result in improved overall survival (OS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) (confirmed centrally) following complete resection and standard post-operative therapy.
SECONDARY OBJECTIVES:
I. To assess whether adjuvant therapy with erlotinib will result in improved disease free survival (DFS) over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.
II. To evaluate the safety profile of erlotinib in the adjuvant setting. III. To assess whether adjuvant therapy with erlotinib will result in improved DFS rate at 2 years, and OS rate at 5 and 10 years over observation for patients with completely resected stage IB (>= 4 cm)-IIIA EGFR mutant NSCLC (confirmed centrally) following complete resection and standard post-operative therapy, both overall and within the stage subgroups: IB and II/IIIA.
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
盲法说明
As of June 15, 2017, sites will sign into RAVE to unblind any patients that had previously enrolled
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
- •Previously registered to A151216, with the result of lung cancer harboring an EGFR exon 19 deletion or L858R mutation; the testing must have been performed by one of the following criteria:
- •Patient registered to A151216 and the assessment performed centrally by the protocol-specified laboratory
- •By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the report must indicate the result as well as the CLIA number of the laboratory that performed the assay; these patients will also have been registered to A151216, but can be enrolled on A081105 regardless of the central lab results
- •Patients with known resistant mutations in the EGFR tyrosine-kinase (TK) domain (T790M) are not eligible
- •Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK) rearrangements will be registered to A081105
- •Completely resected stage IB (>= 4 cm), II or IIIA non-squamous NSCLC with negative margins; patients may not have received neoadjuvant therapy (chemo- or radio-therapy) for this lung cancer
- •Complete recovery from surgery and standard post-operative therapy (if required); patients must be completely recovered from surgery at the time of randomization; the minimum time requirement between date of surgery and randomization must be at least 28 days, the maximum time requirement between surgery and randomization must be 90 days if no adjuvant chemotherapy was administered, 240 days if adjuvant chemotherapy was administered, and 300 days if adjuvant chemotherapy and radiation therapy was administered
- •Age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •No locally advanced or metastatic cancer requiring systemic therapy within 5 years prior to registration; no secondary primary lung cancer diagnosed concurrently or within 2 years prior to registration
- •Non-pregnant and non-lactating
- •No history of cornea abnormalities
- •Granulocytes >= 1,500/ul
- •Platelets >= 100,000/ul
- •Total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT) =< 1.5 x ULN
- •Serum creatinine =< 1.5 x ULN
排除标准
- 未提供
研究组 & 干预措施
Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
干预措施: Clinical Observation (Other)
Arm D (observation)
Patients (including patients previously randomized to placebo) undergo observation at least every 6 months for 2 years.
干预措施: Laboratory Biomarker Analysis (Other)
Arm C (unblinded erlotinib hydrochloride)
Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Erlotinib Hydrochloride (Drug)
Arm A (blinded erlotinib hydrochloride)
Blinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Erlotinib Hydrochloride (Drug)
Arm C (unblinded erlotinib hydrochloride)
Unblinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Arm B (placebo)
Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Placebo Administration (Other)
Arm B (placebo)
Patients receive placebo PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Laboratory Biomarker Analysis (Other)
Arm A (blinded erlotinib hydrochloride)
Blinded patients receive erlotinib hydrochloride PO QD on days 1-21. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. (CLOSED 06/14/17)
干预措施: Laboratory Biomarker Analysis (Other)
结局指标
主要结局
Overall survival (OS)
时间窗: The time from randomization until death, assessed up to 10 years
Estimated using the method of Kaplan-Meier survival curves and a 1-sided stratified log rank test (accounting for all the stratification factors) will be used to compare OS between the two arms. Cox proportional hazards model (including time varying coefficients as necessary) will be used to assess whether the distribution of OS times differ with respect to treatment regimen after having adjusted for the stratification factors as well as other potential prognostic and treatment covariates.
次要结局
- Overall survival (OS) rate at 10 years(At 10 years)
- Disease free survival (DFS) rate(Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed at 2 years)
- Overall survival (OS) rate at 5 years(At 5 years)
- Overall disease free survival (DFS) between the erlotinib hydrochloride and observation arms(Time from randomization until documented disease-recurrence or death, whichever occurs first, assessed up to 10 years)
- Incidence of adverse events associated with each treatment arm(Up to 10 years)