NCT03653546已完成2 期
A Randomized, Open-label, Controlled, Multi-Center Phase II/III Study to Assess the Efficacy and Safety of AZD3759 vs. a Standard of Care EGFR TKI, as First Line Treatment to EGFR Mutation Positive Advanced NSCLC With CNS Metastases
Alpha Biopharma (Jiangsu) Co., Ltd.6 个研究点 分布在 4 个国家目标入组 492 人开始时间: 2018年10月29日最近更新:
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 492
- 试验地点
- 6
- 主要终点
- PFS assessed by Blinded Independent Central Radiological
研究概览
简要总结
The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced EGFR mutation positive non-small cell lung cancer (NSCLC) with Central Nervous System (CNS) metastasis
详细描述
This is a Phase II/III randomized, open-label, multicenter study to compare the efficacy and safety of first line single-agent AZD3759 vs. Erlotinib or Gefitinib treatment in patients with advanced EGFR mutation positive NSCLC with CNS metastases.
Eligible patients with documented EGFR mutation+ (L858R and/or Exon 19Del) TKI-naïve advanced NSCLC and documented intracranial disease will be enrolled.
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
- •Properly completed patient informed consent
- •Male or female aged at least 18 years
- •Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR mutations including L858R and/or Exon19Del. EGFR mutation status will be determined by local or central laboratory testing on tumour tissue or plasma utilizing a validated methodology which has been approved by the regulatory authority.
- •No prior treatment with chemotherapy, EGFR-TKIs, or biological therapies that are considered first line treatment for advanced NSCLC.
- •All patients must have a documented diagnosis of advanced (Stage IV) NSCLC with Magnetic Resonance Imaging (MRI) documented CNS metastases that include brain metastases (BM). BM + patients with co- existent leptomeningeal involvement are eligible for the study.
- •Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
- •All patients must be stable without any systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
- •Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks.
- •Women of child-bearing potential and male subjects shall agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All women of child-bearing potential must have a negative blood pregnancy test at screening.
- •(a) For Patients with measurable CNS lesions must have AT LEAST ONE site of CNS lesion, which was not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter by MRI and which is suitable for accurate repeated measurements. Measurable extracranial disease is not required. (b) For Patients with non-measurable CNS lesions must have AT LEAST ONE extracranial lesion, which has not been previously irradiated, within the screening period that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) by CT/MRI and are suitable for accurate repeated measurement.
排除标准
- 未提供
研究组 & 干预措施
AZD3759 Group
Experimental
AZD3759 group will receive a 200 mg twice daily dose of AZD3759
干预措施: AZD3759 (Drug)
Erlotinib or Gefitinib Group
Active Comparator
SoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
干预措施: Erlotinib (Drug)
Erlotinib or Gefitinib Group
Active Comparator
SoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
干预措施: Gefitinib (Drug)
结局指标
主要结局
PFS assessed by Blinded Independent Central Radiological
时间窗: 48 months
To assess if first line treatment with AZD3759 results in significant PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using RECIST 1.1.
次要结局
- Overall ORR assessed by investigator using RECIST 1.1(48 months)
- DoR for Intracranial lesions assessed by investigator using RANO-BM(48 months)
- Disease Control Rate (DCR) assessed by investigator using RECIST 1.1(48 months)
- Duration of Response (DoR) assessed by investigator using RECIST 1.1(48 months)
- Overall DCR assessed by investigator using RECIST 1.1(48 months)
- Body temperature assessed during the study period.(48 months)
- Number of participants with treatment-related Serious Adverse Events as assessed by CTCAE v5.0(48 months)
- Overall Survival(48 months)
- Neurological function improvement rate assessed by Mini-Mental Status Examination (MMSE)(48 months)
- Incidence of laboratory abnormalities collected by hematology tests during the study as assessed by CTCAE v5.0(48 months)
- PFS assess by BICR(48 months)
- Intracranial PFS (iPFS) assessed by BICR(48 months)
- Extracranial PFS (ePFS) assessed by investigator(48 months)
- Extracranial PFS (ePFS) assessed by BICR(48 months)
- Overall DoR assessed by investigator using RECIST 1.1(48 months)
- ORR for Intracranial lesions assessed by investigator using RANO-BM(48 months)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire BN20 (EORTC QLQ-BN20).(48 months)
- Neurological function improvement rate assessed by RANO-BM criteria(48 months)
- Incidence of laboratory abnormalities collected byurinalysis tests during the study as assessed by CTCAE v5.0(48 months)
- Rhythm, PR, R-R, QRS and QT intervals and an overall evaluation of ECG assessed during the study period.(48 months)
- PFS assess by investigator(48 months)
- Intracranial PFS (iPFS) assessed by investigator(48 months)
- Objective Response Rate (ORR） assessed by investigator using RECIST 1.1(48 months)
- DCR for Intracranial lesions assessed by investigator using RANO-BM(48 months)
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30).(48 months)
- Number of participants with treatment-related Adverse Events as assessed by CTCAE v5.0(48 months)
- Incidence of laboratory abnormalities collected by biochemistry tests during the study as assessed by CTCAE v5.0(48 months)
- Systolic and Diastolic Blood Pressure assessed during the study period.(48 months)
- Pulse rate assessed during the study period.(48 months)
研究者
研究点 (6)
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