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AZD2014 and Weekly Paclitaxel in Squamous NSCLC

2018年6月4日 更新者：AstraZeneca

A Phase 2a, Multi-centre, Single-arm Trial of the Combination of AZD2014 and Weekly Paclitaxel in Patients With Relapsed or Refractory Squamous Non-Small Cell Lung Cancer After At Least One Line of Prior Therapy

Open--label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC)

研究概览

地位

终止

条件

干预/治疗

详细说明

This is an open-label, phase 2a, multi-centre, single-arm study to assess the efficacy and safety of the combination of AZD2014 and weekly paclitaxel in patients with squamous non-small cell lung cancer (NSCLC) that is relapsed or refractory to conventional treatment after at least 1 prior treatment with standard of care (SOC) and for whom weekly paclitaxel treatment is an appropriate treatment choice.

The study will simultaneously enrol patients to the following two groups. Group A (intensive PK) will enrol 10 evaluable patients for an intra-patient evaluation of the impact of paclitaxel on exposure to AZD2014, and the impact of AZD2014 on exposure to paclitaxel via intensive PK sampling and non-compartmental PK analysis techniques (NCA). Group B (sparse PK) will enrol 30 patients and sparse sampling and population PK modelling techniques will be employed to estimate exposure to AZD2014 when administered in combination with a weekly paclitaxel dosing regimen. The efficacy and safety of the AZD2014 and weekly paclitaxel combination will be evaluated in all 40 patients using RECIST 1.1, observation of AEs/SAEs and use of conventional safety parameters.

Eligible patients will receive study treatment consisting of a single weekly paclitaxel infusion (80 mg/m2) on Day 1 of each week and twice daily (BD) 50 mg doses of AZD2014 on the first 3 days each week for 6 weeks [except Group A patients in Week 1 of Cycle 1 who will take 50 mg BD doses of AZD2014 on Days 3, 4 and 5 (or Days 4, 5 and 6) to accommodate PK sampling], followed by a break from treatment when no paclitaxel or AZD2014 will be given. This 7-week schedule composes one cycle of treatment. AZD2014 will be administered as oral tablets to fasted patients (i.e., no food 2 hours before and 1 hour after each dose). Patients will receive up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator.

研究类型

介入性

注册 (实际的)

11

阶段

  • 阶段2

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

  • 德国
      • Gauting、德国、82131
        • Research Site
  • 美国
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Research Site
    • Michigan
      • Detroit、Michigan、美国、48201
        • Research Site
    • Pennsylvania
      • Hershey、Pennsylvania、美国、17022
        • Research Site
    • Texas
      • Dallas、Texas、美国、75251
        • Research Site
  • 西班牙
      • Barcelona、西班牙、08035
        • Research Site
      • Girona、西班牙、17007
        • 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 130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:

  1. Histologically or cytologically proven squamous non-small cell lung cancer (NSCLC) where treatment with weekly paclitaxel is an appropriate treatment option.
  2. Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment.
  3. Measurable disease by RECIST v1.1 criteria
  4. Life expectancy of at least 12 weeks.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

  1. Radiotherapy (except for palliative reasons), chemotherapy, endocrine therapy, or immunotherapy during the previous 3 weeks (4 weeks for investigational medicinal products and 6 weeks for nitrosoureas and Mitomycin-C) before treatment.
  2. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or Grade 1 toxicities which, in the opinion of the Investigator, should not exclude the patient.
  3. Known leptomeningeal involvement, brain metastases or spinal cord compression.
  4. History of hypersensitivity (> Grade 2) to active or inactive excipients of AZD2014, drugs containing Cremophor, taxanes or structurally/chemically similar drugs
  5. Current refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow formulated product or previous significant bowel resection that would preclude adequate absorption of AZD2014
  6. Patients with Diabetes Type I or uncontrolled Type II (HbA1c > 59 mmol/mol assessed locally) as judged by the Investigator
  7. Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study and from which the patient has not yet recovered

  8. Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening (with the exception of pegylated G-CSF (pegfilgrastim) and darbepoetin which require at least 14 days prior to screening), defined as:

    • Absolute neutrophil count 1500 cells/mm3 (1.5 x 109/L)
    • Platelet count 100.000 cells/mm3 (100 x 109/L)
    • Haemoglobin 9.0 g/dL

  9. Adequate hepatic and renal function defined as:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) 2.5 x upper limit of normal (ULN) if no demonstrable liver metastases or 5 x ULN in the presence of liver metastases
    • Alkaline phosphatase (ALP) < 5 x ULN
    • Serum bilirubin 1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
    • Estimated Creatinine Clearance 50 ml/min (Cockcroft-Gault) or serum creatinine 1.5 x ULN

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：Open-label AZD2014
Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel
药品：Open-label AZD2014
Dual TORC1/TORC2 inhibitor
药品：paclitaxel
Taxane

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
Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes
大体时间：From first dose until disease progression (Approximately 3 months)
Calculation of the percentage of patient who have a Complete Response or Partial Response to treatment which is confirmed by a repeat assessment 4 weeks later
From first dose until disease progression (Approximately 3 months)

次要结果测量

结果测量
措施说明
大体时间
Number of Patients Who Experienced at Least One Adverse Event (AE) or Serious Adverse Event (SAE)
大体时间：Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)

The safety and tolerability of AZD2014 with weekly paclitaxel as assessed with the collection of Adverse Events and Serious Adverse Events as reported during clinic visits. In addition, clinical assessments were made throughout the on treatment period including blood test for chemistry, haematology, and blood clotting. In addition to clinical observations such as vital signs, and cardiac function through the use of ECG.

Any findings from the above assessments which were considered to be abnornal and clinically significant by the doctor were reported as (AEs or SAEs).
Informed consent until end of safety follow up (Approx 10 months if all treatment cycles are completed)
Overall Survival: Median Number of Days Between the First Dose and End of Life Due to Any Cause
大体时间：From first dose until end of life (Approx 9 months)
Assessment of the duration of overall survival in weeks through direct patient follow-up. Any patient not known to have died at the time of analysis censored at the last recorded date the patient was known to be alive
From first dose until end of life (Approx 9 months)
Best Objective Response: Number of Patients Who Experienced a Best Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not-Evaluable (NE), Through Measurement of Tumour Lesion Sizes.
大体时间：From Baseline until Disease Progression (Approx 3 months)
Per Response Evaluation Criteria In Solid Tumours (RECIST v1.1) for target lesions assessed through imaging (CT or MRI scan) or clinical examination; Complete Response (CR): Disappearance of all target lesions; Partial Response (PR) >=30% decrease in sum of target lesion longest diameter; Progressive Disease >=20% increase in sum of target lesion longest diameter; Stable Disease (SD) increase or decrease amounting to neither PR or PD. Overall tumour assessment based on quantitative assessment of target lesions and qualitative assessment of non-target lesions in line with RECIST criteria.
From Baseline until Disease Progression (Approx 3 months)
Duration of Response: Median Number of Days From the Date of First Documented Response Until the Date of Documented Progression Through Measurement of Tumour Lesion Sizes
大体时间：From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)
Assessment of the duration of tumour response through assessment of tumour lesions by RECIST 1.1 criteria. Response is defined as the point at which the criteria for Partial Response (PR) was met) >=30% decrease in sum of target lesion longest diameter. Progression is defined as the point at which the criteria for Progressive Disease (PD) was met >=20% increase in sum of target lesion longest diameter, or until end of life.
From date of first documented response until documented progression or end of life in the absence of progression (Approx 3 months)
Disease Control Rate: Percentage of Patients Who Achieve Partial Response, Complete Response or Stable Disease Through Assessment of Tumour Lesion Sizes
大体时间：From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks
Assessment of the disease control rate, percentage of patients who experience a response through assessment of tumour lesions by RECIST 1.1 criteria
From first dose until documented progression and at least 6 weeks after the start of treatment for assessment of Stable Disease - Assessed at 6, 13 and 20 Weeks
Change in Tumour Size: Median Percentage Change in Tumour Size in mm by Measurement of Tumour Lesion Sizes
大体时间：From baseline until documented progression (Approx 3 months)
Assessment of the degree of tumour response through measurement of the change in tumour lesion sizes
From baseline until documented progression (Approx 3 months)
Progression Free Survival: Median Number of Days Between Start of Dosing Until Objective Disease Progression Through Measurement of Tumour Lesion Sizes
大体时间：From date of first dose until documented progression or end of life (Approx 3 months)
Assessment of the duration of progression free survival through assessment of tumour lesions by RECIST 1.1 criteria
From date of first dose until documented progression or end of life (Approx 3 months)
Evaluate the Effect of the Combination of AZD2014 and Paclitaxel on Pharmacokinetics Assessment of Cmax
大体时间：Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8
To determine the effect of co-administration of paclitaxel on the PK of oral AZD2014 and the effect of co administration of oral AZD2014 on the PK of paclitaxel (Group A) by: PK parameters for each in the presence and absence of the other by intensive PK sampling and NCA techniques.
Assessment at multiple timepoints in Group A patients. Samples will be taken at pre-dose and at 10 further timepoints on day 1 and at pre-dose and 9 further timepoints on days 3 and 8
Estimated Pharmacokinetic Exposure to AZD2014 Through the Use of Population PK Modelling
大体时间：Assessment at multiple timepoints in Group B patients between study day 1 and day 3. Samples will be taken at 3 points on day 1 and at predose and at a further 2 points on day 3
Group B patients: PK parameters for AZD2014 estimated from a sparse PK sampling regimen and use of population PK modelling techniques (may be reported outside the clinical study report (CSR))
Assessment at multiple timepoints in Group B patients between study day 1 and day 3. Samples will be taken at 3 points on day 1 and at predose and at a further 2 points on day 3

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

  • 首席研究员：Chandra P Belani, MD、Hershey Medical Center

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)

2015年4月15日

初级完成 (实际的)

2016年12月29日

研究完成 (实际的)

2016年12月29日

研究注册日期

首次提交

2015年3月7日

首先提交符合 QC 标准的

2015年3月26日

首次发布 (估计)

2015年3月31日

研究记录更新

最后更新发布 (实际的)

2018年7月3日

上次提交的符合 QC 标准的更新

2018年6月4日

最后验证

2018年6月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • D2274C00001

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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