A Phase 1 Study of ABT-767 in BRCA1 or BRCA2 Mutation Carriers With Advanced Solid Tumors and in Subjects With High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 93
- 试验地点
- 3
- 主要终点
- Pharmacokinetic profile
研究概览
简要总结
This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced Breast Cancer 1 or 2 gene (BRCA1 or BRCA2)-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
详细描述
This is a Phase 1, dose escalation trial evaluating the tolerability, pharmacokinetics, and pharmacodynamics of ABT-767 in subjects with advanced BRCA1 or BRCA2-mutated solid tumors and high grade serous ovarian, fallopian tube, or primary peritoneal cancer. ABT-767 is a potent oral inhibitor of the enzymes poly (ADP-ribose) polymerase 1 and 2 (PARP-1 and PARP-2). Malignancies with deficiencies in homologous repair, such as BRCA-1 and BRCA-2 deficient tumors, are more dependent on PARP for deoxyribonucleic acid (DNA) repair than normal cells and, thus, are thought to be more sensitive to PARP inhibition. The study design is a single-arm dose escalation study to determine dose-limiting toxicities, maximum tolerated dose and the recommended Phase 2 dose (RPTD) of orally administered ABT-767 in subjects with BRCA mutations and malignancies. In order to further evaluate the safety and tolerability of ABT-767 at the RPTD, 20 additional subjects will be enrolled in an expanded safety cohort consisting of BRCA1- or BRCA2-mutated Breast cancer and Ovarian cancer.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be ≥ 18 years of age.
- •Subjects must have histological or cytological confirmation of locally advanced or metastatic solid tumor, and a documented Breast Cancer Gene 1 or 2 mutation, or high grade serous ovarian, fallopian tube, or primary peritoneal cancer.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 2
- •Subjects must have adequate hematologic, renal, and hepatic function as follows: a. Bone Marrow: Absolute neutrophil count (ANC ≥ 1,500/mm3 (1.5 ≥ 109/L); Platelets ≥ 100,000/mm3 (100 ≥ 109/L); Hemoglobin ≥ 9.0 g/dL (1.4 mmol/L) (hemoglobin unsupported by transfusion b. Subject has adequate renal function as demonstrated by serum creatinine value of ≤ 1.5 x the upper limit of normal (ULN) and either an estimated creatinine clearance value of ≥ 50 mL/min as determined by the Cockcroft-Gault formula or a creatinine clearance value of ≥ 50 mL/min/1.73 m2 based on a 24-hour urine collections c. Subject has adequate liver function as demonstrated by serum bilirubin ≤ 1.5 x ULN and Aspartate Aminotransferase (AST) and Alanine Transaminase (ALT) ≤ 2.5 ULN. For subjects with liver metastasis, AST and ALT < 5 x ULN. Partial Thromboplastin Time (PTT) must be ≤ ULN and INR < 1.
- •Subjects on anticoagulant (such as Coumadin) are allowed on study and will have PTT and International Normalize Ratio (INR) as determined by the Investigator.
- •Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of the study participation, and for 90 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and a negative urine pregnancy test on the first day of study drug administration. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
排除标准
- •Expanded cohort only: Subject has previously received a poly (ADP-ribose) polymerase (PARP) inhibitor.
- •Subject has received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within a period of 28 days or 5 half lives (whichever is shorter) prior to Study Day
- •Subject has known Central Nervous System (CNS) metastases.
- •Subject has unresolved toxicities from prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (CTCAE v 4.0) grade 2 or higher clinically significant toxicity (excluding alopecia).
- •Subject has had major surgery within 28 days prior to Study Day
- •Clinically significant uncontrolled condition(s) or any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities.
- •Psychiatric illness/social situation that would limit compliance with study requirements.
- •Lactating or pregnant female.
研究组 & 干预措施
ABT-767
ABT-767 monotherapy
干预措施: ABT-767 (Drug)
结局指标
主要结局
Pharmacokinetic profile
时间窗: Various time points from Cycle 1 Day -4 to Day 8
Blood samples for pharmacokinetics of ABT-767 will be collected at designated time points
次要结局
- Safety (number of subjects with adverse events and/or dose limiting toxicities)(Weekly for the first two months, every other week for the third month, and monthly there after. An expected average is 5 months.)