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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes
研究概览
简要总结
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)
详细描述
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven squamous non-small cell lung cancer (NSCLC) where treatment with weekly paclitaxel is an appropriate treatment option.
- •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.
- •Measurable disease by RECIST v1.1 criteria
- •Life expectancy of at least 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •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.
- •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.
- •Known leptomeningeal involvement, brain metastases or spinal cord compression.
- •History of hypersensitivity (> Grade 2) to active or inactive excipients of AZD2014, drugs containing Cremophor, taxanes or structurally/chemically similar drugs
- •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
- •Patients with Diabetes Type I or uncontrolled Type II (HbA1c > 59 mmol/mol assessed locally) as judged by the Investigator
- •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
- •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
- •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
研究组 & 干预措施
Open-label AZD2014
Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel
干预措施: Open-label AZD2014 (Drug)
Open-label AZD2014
Open-label AZD2014 given twice daily 3 days on, 4 days off during weekly paclitaxel
干预措施: paclitaxel (Drug)
结局指标
主要结局
Percentage of Patients Who Have a Partial Response or Complete Response Through Measurement of Tumour Lesion Sizes
时间窗: 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
次要结局
- Number of Patients Who Experienced at Least One Adverse Event (AE) or Serious Adverse Event (SAE)(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(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.(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(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(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(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(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(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(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)