An Open-Label,Single-Arm,Phase I Clinical Trial to Evaluate the Pharmacokinetics,Safety and Tolerability of ZL-2306 (Niraparib) in Patients With Ovarian Cancer,Fallopian Tube Cancer and Primary Peritoneal Cancer (Collectively Termed as Ovarian Cancer)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 6
- 主要终点
- The plasma drug concentration before drug administration
研究概览
简要总结
Niraparib is a potent and highly selective PARP-1/-2 inhibitor. The primary objective of this trial is to evaluate the pharmacokinetic (PK) properties of ZL-2306 (niraparib) and its metabolite M1 in patients from Mainland China with ovarian cancer, following a single and multiple oral administration of the study drug at the indicated dose (300mg, 200mg or 100mg), once a day.
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent .
- •Female, age ≥ 18 years.
- •Histologically confirmed diagnosis of FIGO stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
- •Has received no further than second-line platinum-based chemotherapy, and has clinical complete response (CR) or partial response (PR) at least following 4 courses of the last platinum-based chemotherapy.
- •Has good organ function, including:
- •Patient of childbearing potential, has a negative pregnancy test when enrolled and promises to use an adequate method of contraception or abstain from activities that could result in pregnancy from enrolment to the end of study and during the 3 months after the last dose of the study treatment, or be of non-childbearing potential, can be enrolled in the study.
- •Is able to adhere to the protocol.
- •Has recovered from previous chemotherapy induced toxic side effects to ≤ grade 1 CTCAE or basal level, apart from ≤ grade 2 CTCAE peripheral neuropathy or hair loss symptoms at steady state.
排除标准
- •Has a known hypersensitivity to the active or inactive ingredients of ZL-2306 (niraparib) or compound which has similar chemical structure to ZL-2306 (niraparib).
- •Has symptomatic uncontrolled brain or leptomeningeal metastasis.
- •Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
- •Receive palliative radiotherapy encompassing > 20% of the bone marrow within 1 week of entering the study.
- •Be diagnosed any invasive cancer other than ovarian cancer (apart from cured basal cell carcinoma and squamous cell carcinoma) within 2 years prior to study enrolment.
- •Has a history or current diagnosis of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
- •Has other serious or uncontrolled disease
- •Has any disease, treatment and laboratory abnormality that may interfere the study results and affect the fully attendance of study. Or the patient is considered to be not suitable for the study by the investigator. Cannot receive platelet or red blood cell transfusion within 4 weeks of study drug administration.
- •Pregnant, breastfeeding or expecting to conceive children during the study treatment period.
- •Corrected QT (QTc) interval > 470 msec.
- •Use proton pump inhibitors, antacids or histamine 2 (H2) blockers within 48hrs prior to the first drug administration for PK measurement.
研究组 & 干预措施
ZL-2306 (niraparib)
Subjects will be randomised into 100mg, 200mg, 300mg dose group at the first day of the first cycle.
干预措施: ZL-2306 (niraparib) (Drug)
结局指标
主要结局
The plasma drug concentration before drug administration
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Elimination half-life (t1/2)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Time to reach Css max (Tss max)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Steady-state apparent total body clearance of drug from plasma (Clss/F)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Accumulation ratio following multiple drug administration (RAC)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Apparent total body clearance of the drug from plasma (CL/F)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Apparent volume of distribution (Vd/f)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Mean residence time (MRT)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Minimum plasma drug concentration at steady-state (Css min)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero to the end of drug administration (AUCss)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Terminal rate constant (λz)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Degree of fluctuation (DF)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Maximum plasma drug concentration at steady-state (Css max)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Maximum plasma drug concentration (Cmax)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Time to reach Cmax (Tmax)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero to 24hrs (AUC (0-24))
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
Area under the plasma concentration-time curve from time zero to time of last measurable concentration (AUC(0-t)) and from zero to infinity (AUC0-∞)
时间窗: From pre-dose to day 1 of the 2nd cycle (each cycle is 28 days)
次要结局
- Number of participants with adverse events as assessed by CTCAE v4.0(From the signing of ICF till the end of this study (30 days after the last administration of the study drug or the date to close the clinical trial database, whichever is earlier))