NCT02504346进行中（未招募）2 期
AZD9291, an Irreversible EGFR-TKI, in Relapsed EGFR-mutated Non-small Cell Lung Cancer Patients Previously Treated With an EGFR-TKI, Coupled to Extensive Translational Studies
Oslo University Hospital7 个研究点 分布在 5 个国家目标入组 200 人开始时间: 2015年8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
- 进行中（未招募）
- 发起方
- 入组人数
- 200
- 试验地点
- 7
- 主要终点
- Objective response rate
研究概览
简要总结
Phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg, orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally advanced or metastatic NSCLC, who have progressed following treatment with an approved epidermal growth factor tyrosine kinase inhibitor agent.
详细描述
This is a phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg, orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally advanced or metastatic NSCLC, who have progressed following treatment with an approved epidermal growth factor tyrosine kinase inhibitor agent.
If feasible, subjects will have to provide a biopsy sample for molecular testing following confirmed disease progression on the most recent treatment regimen. A second biopsy will be sampled at progression on AZD9291, if feasible. Liquid biopsies will be sampled throughout the treatment period.
Subjects should continue on study treatment until RECIST 1.1-defined progression or until a treatment discontinuation criterion is met. There is no maximum duration of treatment as subjects may continue to receive investigational product beyond RECIST 1.1 defined progression as long as they are continuing to show clinical benefit, as judged by the investigator.
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
- •Provision of signed and dated, written informed consent.
- •Age > 18 years.
- •Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy.
- •Radiological disease progression following at least one prior EGFR TKI.
- •Documented EGFR mutation known to be associated with EGFR TKI sensitivity (also including T790M).
- •ECOG status 0-2 and a minimum life expectancy of 12 weeks.
- •At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.
- •Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- •Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- •Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
- •Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- •Male subjects must be willing to use barrier contraception.
排除标准
- •Treatment with an EGFR-TKI within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment.
- •Treatment with cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment.
- •Previous treatment with AZD9291, or another EGFR TKI with similar profile, e.g. CO-1686
- •Major surgery within 4 weeks of inclusion
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of inclusion
- •Subjects currently receiving (or unable to stop using) potent inhibitors or inducers of CYP3A4
- •Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.
- •Spinal cord compression or brain metastases unless asymptomatic and on stable steroid dosage for at least 2 weeks prior to start of study treatment.
- •Any evidence of severe or uncontrolled systemic diseases which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
- •Gastrointestinal conditions incompatible with swallowing or precluding absorption of AZD
- •Exclude based on any of the following cardiac criteria:
- •Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
- •Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
- •Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval
- •Current or previous significant interstitial lung disease or radiation pneumonitis
- •Absolute neutrophil count < 1.5 x 109/L
- •Platelet count < 100 x 109/L
- •Haemoglobin < 80 g/L
- •Alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
- •Aspartate aminotransferase (AST) > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
- •Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases
- •Creatinine >1.5 times ULN concurrent with creatinine clearance < 50 ml/min (measured or calculated by Cockcroft and Gault equation),
- •History of hypersensitivity of AZD9291 (or drugs with a similar chemical structure or class.
- •Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry
- •Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.
研究组 & 干预措施
Treatment
Experimental
Non-randomized trial, all patients receive therapy - singel-arm
干预措施: AZD9291 (Drug)
结局指标
主要结局
Objective response rate
时间窗: 12 weeks
Measured by RECIST 1.1
次要结局
未报告次要终点
研究者
Odd Terje Brustugun
Senior consultant
Oslo University Hospital
研究点 (7)
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