NCT00491699终止1 期
A Phase 1 Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of XL999 Administered Intravenously to Subjects With Non-Small-Cell Lung Cancer (NSCLC)
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 10
- 主要终点
- Safety, tolerability, and maximum tolerated dose of XL999 administered weekly as a 4-hour intravenous infusion
研究概览
简要总结
The purpose of this study is to determine the safest dose of XL999 and how well subjects with Non-Small-Cell Lung Cancer tolerate XL999. XL999 is a small molecule inhibitor of multiple kinases including VEGFR, PDGFR, FGFR, FLT-3, and Src, which are involved in tumor cell growth, formation of new blood vessels (angiogenesis), and metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 confirmed histological diagnosis of NSCLC.
- •The subject has previously been treated with a platinum- or taxane-containing regimen.
- •The subject has stage IIIB NSCLC with malignant effusion, stage IV or recurrent NSCLC that is not amenable to curative therapy (either surgery or radiation therapy).
- •The subject is at least 18 years old.
- •The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •The subject has a life expectancy of ≥3 months.
- •The subject has adequate organ and marrow function.
- •The subject has cardiac-specific enzyme levels (creatine phosphokinase [CPK] total, CPK-MB, and troponin) below the institution's ULN.
- •The subject is capable of understanding the protocol and has signed the informed consent document.
- •Sexually active subjects (male and female) must use medically accepted methods of contraception during the entire course of the study.
- •Female subjects of childbearing potential must have a negative pregnancy test at enrollment.
- •If a subject has received more than three prior regimens of cytotoxic chemotherapy, or more than two biological or targeted therapies, or more than 3000 cGy to >25% of his or her bone marrow, the investigator must discuss with the sponsor regarding subject suitability prior to enrollment.
- •The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed ≥5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).
排除标准
- •The subject has received systemic anticancer therapy (eg, chemotherapy, biologic therapy, targeted therapy, cytokines, or hormones) within 14 days before the first dose of study drug.
- •The subject has received radiation to >25% of his or her bone marrow within 30 days of XL999 treatment.
- •The subject has not recovered to Grade ≤1 from adverse events (AEs) due to investigational or other agents administered more than 14 days prior to study enrollment.
- •The subject has history of or known brain metastases, current spinal cord compression, or carcinomatous meningitis.
- •The subject is known to be positive for the human immunodeficiency virus (HIV).
- •The subject has uncontrolled and/or intercurrent illness including but not limited to the following:
- •Left ventricular ejection fraction (LVEF) assessed by 99mTc multiple-gated acquisition scan (MUGA) is below the institution's lower limit of normal (LLN) at screening. If regional wall motion abnormalities are noted on the MUGA, cardiology consultation should be performed prior to enrollment.
- •History of pulmonary hypertension.
- •History of congestive heart failure (CHF) (New York Heart Association [NYHA] Class II, III, or IV).
- •Active or unstable ischemic disease, including angina pectoris, myocardial infarction, coronary artery bypass grafting (CABG) within the past 12 months.
- •Electrocardiogram (ECG) showing signs of ischemia or myocardial, valvular, or coronary artery disease unless deemed clinically insignificant by a cardiologist.
- •Onset of any changes between the screening ECG and pre-dose ECG unless deemed clinically insignificant by a cardiologist.
- •ECG abnormalities that could cause interpretation difficulties after XL999 administration (eg, left bundle branch block [LBBB], atrial fibrillation, A-V blocks, pacemakers, digoxin).
- •Blood pressure >150/90 mm Hg despite antihypertensive therapy with two medications.
- •Cerebrovascular accident, transient ischemic attack, or evidence of active peripheral vascular disease within 12 months prior to study enrollment.
- •Hematologic:
- •National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 Grade ≥3 hemorrhage within 30 days of study enrollment.
- •Evidence of bleeding diathesis or coagulopathy.
- •Requirement for therapeutic anticoagulation. Patients receiving anticoagulants (eg, warfarin, heparin) will be excluded if international normalized ratio >1.5 or partial thromboplastin time (PTT) >1.5× the institution's ULN.
- •Recent surgical procedures:
- •Major surgery or open biopsy within 30 days of starting treatment with XL
- •Anticipation of major surgical procedure during the study.
- •Wound healing problems:
- •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 30 days prior to treatment.
- •Serious, non-healing wound, ulcer, or bone fracture.
- •Psychiatric illness that would limit compliance with study requirements.
- •The subject is pregnant or breastfeeding.
- •The subject has a known allergy or hypersensitivity to components of the XL999 formulation.
- •The subject is unable or unwilling to abide by the study.
结局指标
主要结局
Safety, tolerability, and maximum tolerated dose of XL999 administered weekly as a 4-hour intravenous infusion
时间窗: Inclusion until 30 days post last treatment
次要结局
- Plasma pharmacokinetics of XL999 administered weekly as a 4-hour intravenous infusion(At various time points during the 4 week Treatment Period and the Treatment Extension Period)
研究者
研究点 (10)
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