A Phase I, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD0156 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Safety and tolerability - Number of patients experiencing adverse events
研究概览
简要总结
The purpose of this study is to determine whether AZD0156 is safe, what is the best dose to give, and how it is processed by the body when given alone or in combination with other agents. The study will also collect some initial information about how effective it is.
详细描述
The study will consist of a number of study modules, each evaluating the safety and tolerability of AZD0156 with a specific combination agent. The combination option may require an initial monotherapy dose escalation to gain an understanding of pharmacokinetics, safety and tolerability before initiating dose escalation in combination. An oral formulation of AZD0156 will be used.
Module 1 explores AZD0156 in combination with olaparib Module 2 explores AZD0156 in combination with irinotecan/FOLFIRI Additional modules may be added to explore AZD0156 as a monotherapy or in combination with other agents and may be in different tumour types.
Expansion cohorts may enroll additional patients to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules, and to get a preliminary assessment of efficacy .
Module 1 includes an expansion cohort in locally advanced/metastatic tumours including but not limited to gastric adenocarcinoma Module 2 includes an expansion cohort in colorectal cancer
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
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
干预措施: Olaparib (Drug)
Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
干预措施: AZD0156 (Drug)
Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
干预措施: irinotecan (Drug)
Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
干预措施: Fluorouracil (Drug)
Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
干预措施: Folinic Acid (Drug)
结局指标
主要结局
Safety and tolerability - Number of patients experiencing adverse events
时间窗: Informed consent until end of Safety Follow-up (approximately 6 months)
Safety and tolerability of AZD0156 alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents as assessed through collection of Adverse Event, Serious Adverse Event, Clinical Chemistry/Haematology/Coagulation/Vital Signs and ECG
次要结局
- Changes in the number of CTCs (Circulating Tumour Cells)(From baseline until 21 days of combination therapy (Approx 6 assessments))
- Measurement of exposure by AUC (Area Under the Curve) calculation(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Overall Survival (Part B Only)(From start of treatment until the end of Long Term Follow-up (Approx 12 months))
- Anti-tumour activity assessed through tumour measurements(Baseline and then every 6 weeks until Safety follow-up (approximately 6 months))
- Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition(From baseline until 21 days of combination therapy (Approximately 11 assessments))
- Changes in the level of total ctDNA (Circulating tumour DNA)(From baseline until 21 days of combination therapy (approximately 11 assessments))
- Measure maximum plasma concentration at steady state (Css max)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Measure time to maximum concentration (tmax)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Measure time to maximum concentration at steady state (tss max)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Measure rate of renal clearance (CLR)(From Baseline until 7 days into treatment period)
- Identification of Maximum Tolerated Dose (MTD)(Informed consent untli end of Dose Limiting Toxicity (DLT) period - Approx 1 month)
- Measure maximum plasma concentration (Cmax)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Measure drug accumulation in the body (RAC)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))
- Measure minimum concentration at steady state (Css min)(From Baseline until 31 days into combination treatment (maximum of 52 timepoints))