A Multicenter, Open-label, Phase 1b Study of TAK-733 (an Oral MEK Inhibitor) in Combination With Alisertib (an Oral Aurora A Kinase Inhibitor) in Adult Patients With Advanced Nonhematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- TAK-733 and alisertib PK parameters including, but not limited to Cmax, Tmax, Area Under Curve (AUC), apparent oral clearance (CL/F), peak-to-trough ratio, and accumulation ratio
研究概览
简要总结
This is a Multicenter, Open-label, Phase 1b Study of TAK-733 in Combination With Alisertib in Adult Patients With Advanced Nonhematologic Malignancies
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
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 18 years or older
- •Patients must have a diagnosis of a solid tumor malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective
- •Radiographically or clinically evaluable tumor
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- •Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse
- •Male patients who agree to practice effective barrier contraception through 4 months after the last dose of alisertib or agree to abstain from heterosexual intercourse
- •Voluntary written consent
- •Clinical laboratory values as specified in the protocol
排除标准
- •Female patients who are breastfeeding and lactating or pregnant
- •Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
- •Treatment with any investigational products within 28 days before the first dose of study drug
- •Prior treatment with Aurora A-targeted agents, including alisertib
- •Prior treatment with MEK inhibitors, including TAK-733
- •Prior treatment with BRAF inhibitors
- •Systemic anticancer therapy within 21 days before the first dose
- •Prior biologic or immunotherapy within 28 days before the first dose
- •Major surgery or serious infection within 14 days before the first dose
- •Life-threatening illness unrelated to cancer
- •Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C
- •Cardiac condition as specified in study protocol or severe CNS, pulmonary, renal or hepatic disease
- •Known GI conditions or GI procedure that could interfere with the oral absorption or tolerance of study drugs
- •History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness
- •History of ongoing or a newly diagnosed eye abnormality
- •Symptomatic brain metastases
- •Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
- •Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons
研究组 & 干预措施
TAK-733 and alisertib
干预措施: TAK-733 and alisertib (Drug)
结局指标
主要结局
TAK-733 and alisertib PK parameters including, but not limited to Cmax, Tmax, Area Under Curve (AUC), apparent oral clearance (CL/F), peak-to-trough ratio, and accumulation ratio
时间窗: Escalation and MTD Refinement: Cycle 1-Day 1, 2, 7, 8, 14,and 15; Tumor Expansion Cohort: Cycle 1-Day 1, 7, 8, and 15; Cycle 2-Day 1, 8,and 15; PK Expansion Cohort: Cycle 1-Day 1, 7, and 8; Cycle 2-Day 7, 14, and 15. Each cycle is a 21 days cycle
To characterize the single- and multiple-dose plasma PK of TAK-733 and alisertib in patients with advanced nonhematologic malignancies
Number of Adverse Events (AEs), Serious Adverse Events (SAEs), assessments of clinical laboratory values, and vital sign measurements
时间窗: From signing of the informed consent form through 30 days after the last dose of study drug
To evaluate the safety profile and to determine DLTs, MTDs, and RP2D of oral TAK-733 + alisertib in patients with advanced nonhematologic malignancies
次要结局
- Measures of disease response, including objective response rate and duration of response based on investigator's assessment using RECIST guidelines(On screening; Cycle 2: between Day 15 and 21, and every third cycle thereafter (5,8,11 etc.) until progressive disease for approximately 1 year)