NCT00997334已完成2 期
First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations
David M. Jackman, MD2 个研究点 分布在 1 个国家目标入组 60 人开始时间: 2010年2月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Resistance Mechanism
研究概览
简要总结
Erlotinib is a drug which targets non small cell lung cancer with a genetic change (mutation) in the epidermal growth factor receptor (EGFR). This drug has been used in other cancer research studies and information from those studies suggests that Erlotinib can control the growth of these cancer cells.
详细描述
PRIMARY OBJECTIVE
-To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib (e.g., T790M mutations, MET amplification).
- Correlate these genetic changes with patient demographic data and clinical outcomes (time to progression, survival, sites of recurrence/progression).
- Search for novel mechanisms of acquired resistance to erlotinib.
- Identify whether these genetic changes are present at low levels in initial pretreatment tumor specimens.
SECONDARY OBJECTIVE(S)
- To measure the steady-state plasma concentrations of erlotinib during the course of patients' treatment.
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 or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible.
- •Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS (the oncogene from the Kirsten rat sarcoma virus) mutations and MET amplification.
- •At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria.
- •18 years of age or older
- •No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
- •3 or more weeks since prior major surgery
- •2 or more weeks since prior radiation
- •ECOG performance status 0-1
- •Life expectancy > 8 weeks
- •Adequate hematologic, renal, and hepatic function
- •Willingness to undergo repeat tumor biopsy at the time of disease progression.
排除标准
- •Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment.
- •More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
- •Prior exposure to erlotinib or other treatments targeting the HER family axis.
- •Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
- •Any process that compromises the ability to swallow and/or absorb oral medication.
- •Incomplete healing from previous surgery
- •A history of any of the following autoimmune skin disorders: Sjogren's syndrome, scleroderma, dermatomyositis, and systemic lupus erythematosus.
- •Significant medical history or unstable medical conditions.
- •Concurrent use of warfarin. Patients must be off warfarin for at least one week prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted.
- •Patients who require ongoing concomitant use of one of the strong inhibitors/inducers of CYP3A
- •Pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
研究组 & 干预措施
Erlotinib
Experimental
Erlotinib was given at a dose of 150mg orally once per day for 28 days (+/- 3 days); Patients are treated until disease progression or until unaccepted drug toxicity.
干预措施: Erlotinib (Drug)
结局指标
主要结局
Resistance Mechanism
时间窗: Participants were evaluated for incidence of genetic mechanisms of secondary resistance at time of disease progression at which point participants stopped treatment. Progression follow up was up to 3 years in this study cohort.
Participants were classified into 4 potential resistant mechanism groups (4 genetic/ 1 histologic) based on evaluation of rebiopsy tissue: EGFR mutations (T790M mutation, exon 20 insertion), KRAS mutations, MET amplification or small-cell lung cancer (SCLC) transform using established methods.
次要结局
- Progression-Free Survival(Disease was evaluated radiologically every 8 weeks on treatment (cycle duration=4 weeks). Participants were treated until evidence of disease progression or unacceptable toxicity. Progression follow-up was up to 3 years in this study cohort.)
研究者
David M. Jackman, MD
Principal Investigator
Dana-Farber Cancer Institute
研究点 (2)
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