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Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer (SELECT-3)

2018年3月12日 更新者：AstraZeneca

A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer (NSCLC)

This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.

This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.

研究概览

地位

完全的

条件

干预/治疗

详细说明

A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)

研究类型

介入性

注册 (实际的)

55

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 英国
      • Glasgow、英国、G12 0YN
        • Research Site
      • London、英国、W1G 6AD
        • Research Site
      • Manchester、英国、M20 4BX
        • Research Site
      • Newcastle upon Tyne、英国、NE7 7DN
        • Research Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 99年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Provision of signed, written and dated consent prior to any study specific procedures
  • Male or female, aged 18 years or older
  • Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
  • Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
  • Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information

Exclusion Criteria:

  • Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
  • Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
  • Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
  • Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
  • As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Selumetinib+standard chemotherapy
Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
药品：selumetinib
2 x 25mg capsules bd continuously in cohort 1 (with gemcitabine and cisplatin). If tolerated - next cohort 3 x 25mg capsules bd continuously. if higher doses are explored, required number of capsules will be provided. Option to administer on D2-19 of each 21 day cycle if required to assess tolerability of combinations with chemotherapy
药品：gemcitabine
1250 mg/m2 iv on Day 1 and 8 of each 21 day cycle. If combination not tolerated, option to give 1000 mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
药品：cisplatin
75 mg/m2 iv on Day 1 of each 21 day cycle. If combination not tolerated, option to give 50 mg/m2 iv on Day 1 or 25mg/m2 iv on Day 1 and Day 8 of each 21 day cycle
药品：carboplatin
If it is not possible to identify a tolerable combination of selumetinib, gemcitabine and cisplatin, cisplatin may be replaced with carboplatin (AUC5) iv on Day 1 of each 21 day cycle
药品：pemetrexed
Gemcitabine may be replaced with pemetrexed 500 mg/m2 iv on Day 1 of each 21 day cycle.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
大体时间：The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks
Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks

次要结果测量

结果测量
措施说明
大体时间
Best Objective Response
大体时间：Screening, week 6 and week 12
The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm
Screening, week 6 and week 12
Percentage Change From Baseline at 6 Weeks in Target Lesion Size
大体时间：Week 6
The percentage change in the sum of the diameters of target lesions
Week 6
Best Percentage Change From Baseline in Target Lesion Size
大体时间：Screening, week 6 and week 12
The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
Screening, week 6 and week 12
Objective Response Rate (ORR)
大体时间：Up until progression or last evaluable assessment in the absence of progression, up to 9 months
The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
Up until progression or last evaluable assessment in the absence of progression, up to 9 months
AUC (0-tau)
大体时间：Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Cmax,ss
大体时间：Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Maximum plasma concentration at steady state
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Tmax,ss
大体时间：Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Time to reach maximum plasma concentration at steady state
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
CL/F
大体时间：Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose
Apparent oral plasma clearance
Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

AstraZeneca

调查人员

  • 研究主任：Gabriella Mariani, MD、AstraZeneca UK, MSD
  • 首席研究员：Emma Dean, BMEDSCI, BM, BS, PHD、The Christie NHS Foundation Trust, UK
  • 首席研究员：Fiona Blackhall, PhD, FRCP、The Christie NHS Foundation Trust Clinical Trials Unit; UK

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2013年4月4日

初级完成 (实际的)

2016年1月4日

研究完成 (实际的)

2016年1月4日

研究注册日期

首次提交

2013年3月8日

首先提交符合 QC 标准的

2013年3月11日

首次发布 (估计)

2013年3月12日

研究记录更新

最后更新发布 (实际的)

2018年3月13日

上次提交的符合 QC 标准的更新

2018年3月12日

最后验证

2018年3月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • D1532C00070
  • EudraCT number: 2012-005202-22

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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