A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered to Japanese Patients With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Safety and tolerability measured by adverse events
研究概览
简要总结
The primary objective of this study is to investigate the safety and tolerability of continuous and/or intermittent dosing of AZD2014 when given orally to patients with advanced solid malignancies.
详细描述
This is an open-label, multi-centre study of AZD2014 administered orally in Japanese patients with advanced solid malignancies. The study design allows an evaluation of each cohort with intensive safety monitoring to ensure the safety of the patients. In this study, a minimum of 3 and a maximum of 6 evaluable patients will be enrolled in each cohort; approximately 24 evaluable patients in total. The total number of patients enrolled will depend upon the number of screen failures, number of cohorts and number of evaluable subjects.
Safety, preliminary efficacy and PK (single and multiple dose) are evaluated in this study.
Patients will receive a single dose of AZD2014 on Day 1 (to allow assessment of single dose PK), then after a minimum of 48 hours washout period continuous or intermittent twice daily dosing of AZD2014 will be initiated. The washout period of 48 hours may be extended depending on emerging data from previous cohorts.Doses and schedules to be evaluated will be agreed by AstraZeneca and the Safety Review Committee (SRC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist
- •For Cohort 3-1 and 3-2, followed as, Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist or where treatment with paclitaxel is an appropriate treatment option. SqNSCLC patients are excluded from the Cohort 3-
- •World Health Organisation (WHO) performance status (PS) 0-1 with no deterioration over the previous 2 weeks prior to informed consent and minimum life expectancy of 12 weeks
- •At least one lesion that can be accurately assessed at baseline by computed tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
- •Exclusion Criteria
- •Prior chemotherapy, biological therapy, radiation therapy, antiandrogens, other anticancer therapies including immunotherapy and any investigational agents within 21 days of starting study treatment (not including palliative radiotherapy at focal sites), or corticosteroids within 14 days of starting study treatment.
- •Major surgery within 4 weeks prior to the study treatment (excluding placement of vascular access), or minor surgery within 2 weeks prior to the study treatment
- •Potent or moderate inhibitors or inducers of cytochrome (CYP) 3A4/5 if taken within the stated washout periods:
- •Potent or moderate inhibitors or inducers of CYP2C8 if taken within the stated washout periods:
- •Exposure to sensitive or narrow therapeutic range substrates of the drug metabolising enzymes CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters P-gp (MDR1), Breast cancer resistance protein (BCRP), Organic anion transporting polypeptide (OATP)1B1, OATP1B3, Organic cation transporter (OCT)1 and OCT2 within the appropriate wash-out period (at least 5 x reported terminal elimination half-life (t1/2) of each drug) before the study treatment.
- •Any haemopoietic growth factors (eg, granulocyte-colony stimulating factor [G-CSF]) within 2 weeks prior to receiving study drug
- •Previous initiation of treatment with AZD2014 in the present study or prior treatment with AZD8055
- •With the exception of alopecia, any unresolved toxicities from prior chemotherapy greater than Common toxicity criteria for adverse events (CTCAE) grade 1 at the time of starting study treatment
- •Spinal cord or brain metastases unless asymptomatic and stable off steroids for at least 4 weeks prior to start of study treatment
- •Subjects with interstitial lung disease as a complication or a history
排除标准
- 未提供
研究组 & 干预措施
AZD2014 50mg, 125mg, 25mg and 50mg intermittent BD
50mg BD continuous dosing, 125mg BD intermittent dosing, 25 mg and 50mg intermittent dosing with weekly Paclitaxel
干预措施: AZD2014 (Drug)
结局指标
主要结局
Safety and tolerability measured by adverse events
时间窗: 6 months in average
This will be assessed in terms of Adverse Events (AEs), laboratory data, vital signs, ECG and physical exams
次要结局
- Cmax of AZd2014(21 days)
- AUC(Area under the plasma concentration-time curve) of AZD2014(21 days)
- Tmax of AZD2014(21 days)
- To obtain a preliminary assessment of the anti-tumour activity of AZD2014 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.(6 months in average)