NCT00055926已完成1 期
A Phase I Safety and Pharmacokinetic/Pharmacodynamic Study of CP-724, 714 In Patients With Metastatic HER2-Overexpressing Breast Cancer
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 2
研究概览
简要总结
RATIONALE: CP-724,714 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.
PURPOSE: Phase I trial to study the effectiveness of CP-724,714 in treating patients who have metastatic HER2-overexpressing breast cancer.
详细描述
OBJECTIVES:
- Determine the safety and tolerability of CP-724,714 in patients with metastatic HER2-overexpressing breast cancer.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine, preliminarily, any antitumor activity of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the relationship of drug-related adverse events to pharmacokinetic exposure parameters in these patients.
- Determine the relationship of changes in serum HER2 extracellular domain and HER2 receptor tyrosine kinase phosphorylation to pharmacokinetic exposure parameters and clinical outcome in patients treated with this drug.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive oral CP-724,714 on days 1 and 3-21 during course 1 and then daily during subsequent courses. Courses repeat every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of CP-724,714 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
研究设计
- 研究类型
- Interventional
- 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
- •Histologically or cytologically confirmed HER2-overexpressing breast cancer
- •Prior or newly documented HER2 amplification by fluorescence in situ hybridization (FISH)
- •Progressive metastatic disease
- •Must have received at least one prior chemotherapy regimen for metastatic breast cancer
- •At least 1 measurable or evaluable lesion
- •At least 1 lesion accessible for 2 separate core biopsies for pharmacodynamic evaluation
- •18 and over
- •Male or female
- •Life expectancy, More than 3 months
- •Hematopoietic
- •Absolute neutrophil count at least 1,500/mm^3*
- •Platelet count at least 100,000/mm^3* NOTE: *Without hematopoietic growth factors or transfusions
- •Bilirubin no greater than 1.5 mg/dL
- •AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- •Creatinine no greater than 1.5 times ULN OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular
- •12-lead ECG with normal tracing
- •history of cardiovascular disease (i.e., ischemic heart disease, arrhythmia, or congestive heart failure) unless asymptomatic for the past year with no requirement for antiarrhythmics or a clinically significant medical management change
- •Gastrointestinal
- •Able to take oral medication* Negative pregnancy test
- •Fertile patients must use effective contraception
- •At least 4 weeks since prior trastuzumab (Herceptin)
- •At least 4 weeks since other prior biologic therapy or immunotherapy
- •At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)
- •At least 6 months since prior doxorubicin or doxorubicin equivalents without any prior or developing signs or symptoms of cardiomyopathy
- •No cumulative doses of more than 300 mg/m^2
- •At least 2 weeks since prior hormonal therapy for the primary disease
- •Concurrent hormone replacement therapy or luteinizing hormone-releasing hormone agonists allowed
- •At least 4 weeks since prior radiotherapy
- •At least 3 weeks since prior major surgery (2 weeks for minor surgery)
- •Recovered from prior therapy
- •At least 4 weeks since prior investigational treatment
- •Coumarin or heparin derivatives allowed for the prevention of deep vein thrombosis or port patency
排除标准
- •known or clinically suspected brain metastases or leptomeningeal disease
- •symptomatic edema or third-space fluid (e.g., ascites or pleural effusions)
- •known hepatitis B or C infection
- •significant ECG changes that require medical intervention
- •QTc interval less than 460 msec
- •No history of torsade or other symptomatic QTc abnormality
- •LVEF greater than 50% by MUGA
- •gastrointestinal abnormality that would require medications (including all antacids)
- •persistent symptoms of an esophageal or digestive disorder
- •pregnant or nursing
- •known HIV infection
- •active infection
- •concurrent uncontrolled systemic disorders or laboratory abnormalities that would preclude study drug safety evaluation
- •mental disorder that would preclude study compliance or ability to give informed consent
- •No more than 2 prior trastuzumab-based regimens for advanced disease
- •concurrent immunotherapy
- •more than 1 prior anthracycline- or anthracenedione-containing regimen (except with approval of the sponsor)
- •prior high-dose chemotherapy with hematopoietic stem cell transplantation
- •concurrent anticancer chemotherapy
- •No concurrent anticancer hormonal therapy, including tamoxifen
- •prior radiotherapy to the only disease site that would be assessed for response
- •concurrent radiotherapy
- •prior partial or complete gastrectomy
- •concurrent antiarrhythmics
- •concurrent antacids
- •concurrent anticoagulant at therapeutic doses
- •other concurrent experimental anticancer medications for breast cancer
研究者
研究点 (2)
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