NCT00704392撤回1 期
A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL647 and XL147 Administered in Combination Daily to Subjects With Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Exelixis
- 试验地点
- 2
- 主要终点
- Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and highest safe doses of XL647 in combination with XL147 in adults with solid tumors. XL647 is a small molecule that potently inhibits multiple receptor kinases, including EGFR, VEGFR2 (KDR), and ErbB2. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells.
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
- •The subject has a histologically confirmed solid tumor that is metastatic or unresectable and is no longer responding to therapies known to prolong survival or to other standard therapies, or has disease for which no standard therapy exists.
- •The subject is ≥ 18 years old.
- •The subject's weight is ≥ 50 kg.
- •The subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •The subject has a life expectancy of ≥ 3 months.
- •The subject has adequate organ and marrow function.
- •The subject has a fasting plasma glucose (FPG) < 120 mg/dL at screening.
- •The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
- •Sexually active subjects (male and female) must agree to use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s).
- •Female subjects of childbearing potential must have a negative pregnancy test at screening.
- •Subjects in the MTD Expansion Cohort:
- •Must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
- •Must have a histologically confirmed diagnosis of NSCLC (Stage IIIB or IV) OR a histologically confirmed diagnosis of metastatic breast cancer.
排除标准
- •The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of XL
- •The subject has received prior treatment with a small molecule kinase inhibitor (including an investigational kinase inhibitor) within 14 days before the first dose of XL
- •The subject has received any other type of investigational agent within 30 days before the first dose of study treatment.
- •The subject has not recovered from toxicity due to prior therapy.
- •The subject has had major surgery within 30 days before the first dose of study drug. Subjects must have recovered or stabilized from prior surgery.
- •The subject is known to have diabetes.
- •The subject is currently receiving anticoagulation with warfarin (low-dose warfarin ≤ 1mg/day, heparin, and low-molecular weight heparins are permitted).
- •The subject has prothrombin time (PT)/International Normalized Ratio (INR) and /or partial thromboplastin time (PTT) test results at screening that are above 1.3 times the laboratory upper limit of normal.
- •The subject has any of the following cardiac criteria:
- •Corrected QT interval (QTc) of > 0.46 seconds
- •Has a finding of left bundle branch block
- •Has important bradycardia defined as a heart rate of < 50 bpm due to sinus node dysfunction
- •Has an obligate pacemaker
- •History of sustained ventricular arrhythmias (subjects with a history of atrial arrhythmias should be discussed with the sponsor before entry into the study)
- •Family history of congenital long QT syndrome or unexplained sudden death
- •Has uncontrolled hypertension
- •Has symptomatic congestive heart failure, unstable angina, or a myocardial infarction within the past 3 months
- •The subject requires treatment with drugs known to be associated with torsades de pointes or significant QT interval prolongation.
- •The subject has a serum potassium level or a serum magnesium level that falls outside the normal range.
- •The subject has known brain metastases or a primary brain tumor.
- •The subject has intercurrent illness including but not limited to ongoing or active infection.
- •The subject is known to be positive for the human immunodeficiency virus (HIV).
- •The subject is pregnant or breastfeeding.
- •The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulations
- •The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
研究组 & 干预措施
1
Experimental
干预措施: XL647 (Drug)
1
Experimental
干预措施: XL147 (Drug)
结局指标
主要结局
Safety, tolerability, and maximum tolerated dose (MTD) of XL647 administered in combination with XL147 orally daily
时间窗: Assessed at periodic visits
次要结局
- Characterize pharmacokinetic parameters of XL647 administered in combination with XL147 daily in subjects with solid tumors(Assessed at periodic visits)
- Assess pharmacodynamic effects of the XL647 and XL147 combination regimen at the highest safe dose of these agents in subjects with non-small-cell lung cancer or breast cancer(Assessed at periodic visits)
研究者
研究点 (2)
Loading locations...
相似试验
终止
1 期
Safety Study of XL844 in Subjects With Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaChronic Lymphocytic LeukemiaNCT00234481Exelixis
已完成
1 期
Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Adults With Solid Tumors or LymphomaCancerLymphomaNCT00486135Sanofi118
已完成
1 期
Study of the Safety and Pharmacokinetics of XL765 (SAR245409) in Adults With Solid TumorsCancerNCT00485719Sanofi83
已完成
1 期
Safety and Pharmacokinetics of XL647 Administered Orally to Subjects With Solid TumorsCancerNCT00086528Kadmon Corporation, LLC41
已完成
1 期
Safety Study of XL147 (SAR245408), in Combination With Paclitaxel and Carboplatin in Adults With Solid TumorsEndometrial CarcinomaOvarian CarcinomaCancerNon-Small Cell Lung CancerNCT00756847Sanofi52