A PHASE I OPEN-LABEL PHARMACOKINETICS AND SAFETY STUDY OF TALAZOPARIB (MDV3800) IN PATIENTS WITH ADVANCED SOLID TUMORS AND NORMAL OR VARYING DEGREES OF HEPATIC IMPAIRMENT
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 38
- 试验地点
- 11
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
研究概览
简要总结
This is a trial to investigate the pharmacokinetics (PK) and the safety of talazoparib in patients with advanced solid tumors and impaired hepatic function.
详细描述
At the end of the study, patients with no clinically significant toxicities, no contraindications to continue treatment with talazoparib, and no disease progression (underlying cancer progression) may be eligible to continue talazoparib treatment in a separate open-label extension study. The decision to allow the patient to continue dosing with talazoparib in an open-label extension (OLE) study will be based on potential overall benefit-risk and patient meeting eligibility criteria for OLE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated Informed Consent Form (by the patient or a legally acceptable representative as per the local regulations).
- •Female or male at least 18 years of age.
- •Histologically or cytologically confirmed advanced solid tumor with no available standard treatment options in the opinion of the Investigator
- •Eastern Cooperative Oncology Group (ECOG) Performance status ≤
- •Expected life expectancy of ≥ 3 months.
- •Able to swallow the study drug (no contraindication to oral agents).
- •Hepatic function at screening and enrollment as defined by the NCI organ dysfunction working group (NCI-ODWG) criteria.
- •Adequate other organ function at screening and enrollment.
- •Female patients of childbearing potential must have a negative serum pregnancy test at screening and must agree to use a highly effective form of contraception from the time of the first dose of study drug through 7 months after the last dose of study drug.
- •Male patients must agree to use a condom when having sex with a pregnant woman or with a non-pregnant female partner of childbearing potential, from 21 days before the first dose of study drug through 4 months after last dose of study drug.
- •Female patients must not be breastfeeding at screening nor during the study participation until 7 months after the last dose of the study drug.
- •Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
排除标准
- •Treatment within 14 days or five half lives prior to enrollment whichever is longer with any type of systemic anticancer-therapy or any investigational drug
- •Have not recovered (recovery is defined as CTCAE grade ≤ 1) from the acute toxicities of previous anticancer standard or investigational therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
- •Major surgery within 28 days prior to enrollment.
- •Serious accompanying cardiac disorder
- •Active known or suspected brain metastasis or active leptomeningeal disease needing treatment
- •Symptomatic or impending spinal cord compression or cauda equine syndrome
- •Has undergone a liver transplant, kidney transplant or nephrectomy.
- •Prior allergic reaction or severe intolerance (meeting the criteria for a serious adverse event, a grade 3 or 4 AE, or permanent treatment discontinuation) to a poly ADP ribose polymerase (PARP) inhibitor.
- •Known myelodysplastic syndrome
- •Seropositive for human immunodeficiency virus (HIV).
- •Any serious or unstable medical condition that interferes with ability to tolerate treatment or assessments associated with the protocol.
- •Gastrointestinal disorder affecting absorption.
- •Known or suspected hypersensitivity to any of the talazoparib capsule components.
- •Any condition or reason that interferes with ability to participate in the study, tolerate treatment or assessments associated with the protocol, causes undue risk, or complicates the interpretation of safety data, in the opinion of the Investigator or Medical Monitor
研究组 & 干预措施
Group A (control, normal hepatic function)
干预措施: Talazoparib (Drug)
Group B (mild hepatic dysfunction)
干预措施: Talazoparib (Drug)
Group C (moderate hepatic dysfunction)
干预措施: Talazoparib (Drug)
Group D (severe hepatic dysfunction)
干预措施: Talazoparib (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 22
时间窗: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 22
时间窗: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
AUC0-24u for unbound talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose. AUC0-24u = fu\*AUC0-24. fu= Fraction of Unbound (fu) Plasma.
Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 22
时间窗: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
AUC0-24 of talazoparib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.
Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 22
时间窗: Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22
Cmaxu was defined as the maximum observed plasma concentration for unbound talazoparib. Cmaxu = fu\*Cmax.
次要结局
- Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24) of Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib on Day 22(Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22)
- Renal Clearance (CLr) of Talazoparib on Day 22(Ae: Post-dose at any time between 0 to 12, 12 to 24 hrs on Day 22; AUC0-24: Pre-dose (24 hrs +/- 60 minutes from previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, any time between 8 to12, 24 hrs post-dose on Day 22)
- Maximum Observed Plasma Concentration (Cmax) of Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Fraction of Unbound (fu) Plasma Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Unbound Area Under the Free Plasma Concentration Time Curve From Zero to 24 Hours (AUC0-24u) of Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Fraction of Unbound (fu) Plasma Talazoparib on Day 22(Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22)
- Apparent Clearance (CL/F) of Plasma Talazoparib on Day 22(Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22)
- Percentage of Talazoparib Excreted in Urine From Time Zero to 24 Hours (Ae 0-24%) on Day 1(A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1)
- Plasma Trough Concentration (Ctrough) of Talazoparib on Day 8, 15 and 22(Pre-dose on Day 8, 15 and 22)
- Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 22(Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 22)
- Accumulation Ratio (Rac) of Plasma Talazoparib(Pre-dose (within 60 minutes prior to dose) on Day 1, pre-dose(24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose) on Day 22 and 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Days 1 and 22)
- Unbound Apparent Clearance (CLu/F) of PlasmaTalazoparib on Day 22(Pre-dose (24 hours +/- 60 minutes from the previous dose on Day 21 but within 60 minutes prior to next dose), 0.5, 1, 2, 4, 6, anytime from 8 to 12 and 24 hours post-dose on Day 22)
- Number of Participants Who Met the Pre-specified 12-Lead Electrocardiogram (ECG) Criteria(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Unbound Maximum Observed Plasma Concentration (Cmaxu) of Talazoparib on Day 1(Pre-dose (within 60 minutes prior to dose), 0.5, 1, 2, 4, 6, anytime between 8 to 12 and 24 hours post-dose on Day 1)
- Amount of Talazoparib Excreted Unchanged in Urine From Time Zero to 24 Hours (Ae 0-24) on Day 1(A single void at pre-dose, post-dose at any time between 0 to 12 and any time between 12 to 24 hours on Day 1)
- Change From Baseline in Vital Sign -Blood Pressure at Day 2, 8, 15, 22 and End of Study(Baseline, Day 2, 8, 15, 22 and End of Study (Day 52))
- Percentage of Talazoparib Excreted in Urine From Time 0 to 24 Hours (Ae 0-24%) on Day 22(Urine voided post-dose at any time between 0 to 12 and any time between 12 to 24 hours (hrs) on Day 22)
- Change From Baseline in Vital Sign- Heart Rate at Day 2, 8, 15, 22 and End of Study(Baseline, Day 2, 8, 15, 22 and End of Study (Day 52))
- Change From Baseline in Vital Sign- Weight at Day 8, 15, 22 and End of Study(Baseline, Day 8, 15, 22 and End of Study (Day 52))
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status(Screening (2 to 28 days prior to Day 1), Day -1 (1 day prior to Day 1), safety follow up (Visit up to Day 52))
- Number of Participants With Clinically Significant Laboratory Abnormalities(Baseline up to 30 days after last dose of study drug (up to 52 days))
- Change From Baseline in Vital Sign- Respiratory Rate at Day 8, 15, 22 and End of Study(Baseline, Day 8, 15, 22 and End of Study (Day 52))