An Open-label, Fixed Sequence Phase I Study to Evaluate the Effect of Itraconazole (a Strong CYP3A Inhibitor) on the Pharmacokinetics of AZ14170132, the TOP1 Inhibitor Payload of the Antibody Drug Conjugate AZD5335, in Participants With Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 9
- 主要终点
- Area under curve from time 0 to time 17 days (AUC0-17days)
研究概览
简要总结
The purpose of this study is to assess the effect of itraconazole on the pharmacokinetics (PK) of AZ14170132.
详细描述
This is a non-randomized, open-label, fixed sequence study to be conducted at multiple study centers.
The study will consist of 2 parts:
Part A of the study will comprise of:
- Screening period
- Treatment period: The treatment period will comprise of Cycles 1, 2 and 3 where the participants will receive AZD5335 along with itraconazole
- Follow-up visit (not applicable for participants involved in Part B)
Part B of the study will comprise of:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants with Platinum-resistant, relapsed, high- grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer and: (a) have received at least 1 prior line of platinum-containing chemotherapy and have progressed on or within 6 months after the date of the last dose of platinum; (b) must have received prior bevacizumab and/or Poly (ADP-ribose) polymerase (PARP) inhibitors according to local guidelines, unless ineligible.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
排除标准
- •Spinal cord compression or a history of leptomeningeal carcinomatosis.
- •Unresolved toxicities of Grade ≥ 2 (National Cancer Institute-Common Terminology Criteria for Adverse Events v5.0) from prior therapy.
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Uncontrolled intercurrent illness within 12 months prior to screening.
- •Any other contraindication for receiving itraconazole according to the prescribing information and the Investigator.
研究组 & 干预措施
AZD5335/AZD5335 + Itraconazole
In Part A, participants will receive AZD5335 alone as an intravenous (IV) infusion, and in combination with oral itraconazole, every 3 weeks (Q3W) from cycle 1 to cycle 3. In Part B, participants will receive AZD5335 as an IV infusion Q3W, from Day 1 of Cycle 4 until progression, unacceptable toxicity or any other specified criteria for discontinuation occurs.
干预措施: AZD5335 (Drug)
AZD5335/AZD5335 + Itraconazole
In Part A, participants will receive AZD5335 alone as an intravenous (IV) infusion, and in combination with oral itraconazole, every 3 weeks (Q3W) from cycle 1 to cycle 3. In Part B, participants will receive AZD5335 as an IV infusion Q3W, from Day 1 of Cycle 4 until progression, unacceptable toxicity or any other specified criteria for discontinuation occurs.
干预措施: Itraconazole (Drug)
结局指标
主要结局
Area under curve from time 0 to time 17 days (AUC0-17days)
时间窗: Cycle 2 and Cycle 3 (each cycle is of 21 days)
The effect of itraconazole on the pharmacokinetics (PK) of AZ14170132 will be assessed.
Maximum plasma drug concentration (Cmax)
时间窗: Cycle 2 and Cycle 3 (each cycle is of 21 days)
The effect of itraconazole on the PK of AZ14170132 will be assessed.
次要结局
- Maximum plasma drug concentration (Cmax)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Area under curve from time 0 to time 17 days (AUC0-17days)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Minimum plasma drug concentration (Cmin)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Area under curve from time 0 to the time of last measurable concentration (AUC0-t)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Terminal elimination (lambda_z)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Half life (t1/2)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Time to maximum observed concentration (tmax)(Cycle 2 and Cycle 3 (each cycle is of 21 days))
- Number of participants with adverse events (AEs) and serious adverse events (SAEs)(Part A: up to 121 days; Part B: up to 365 days post last participant first dose)
- Objective response rate (ORR)(Part A: up to 121 days; Part B: up to 365 days post last participant first dose)
- Duration of response (DoR)(Part A: up to 121 days; Part B: up to 365 days post last participant first dose)
- Progression-free Survival (PFS)(From Day 1 until until disease progression or death (up to 2 years))