Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Median Time to Pleurodesis
研究概览
简要总结
The goal of this clinical research study is to learn the effect of ZD6474 on the amount of time between placement of an indwelling pleural catheter and the catheter's removal in patients with malignant pleural effusion.
This study will also look at the effect that ZD6474 has on tumor cells, biological characteristics of cells in the body, rate of fluid build-up around the lungs, tumor size, and thickness of blood vessels. The effect that this drug has on quality of life and shortness of breath will also be examined.
详细描述
ZD6474 is an investigational drug that has not yet received approval from the FDA. ZD6474 is designed to limit VEGF. Vascular endothelial growth factor (VEGF) is considered to play a key role in the development of pleural effusion. Pleural effusion is an abnormal collection of pleural fluid in the pleural lining surrounding the lungs. The pleural lining is the thin covering that protects and cushions the lungs. It is made up of two layers of tissue that are separated by a small amount of fluid.
ZD6474 has shown promising activity against a number of cancers in laboratory tests in animals with cancer and in some early clinical trials in patients with non-small cell lung cancer (NSCLC). ZD6474 has also demonstrated significant reduction in pleural effusion in association with VEGF inhibition of tumor cells in mice with lung tumors and pleural effusion. It is hoped that ZD6474 will decrease the amount of pleural effusion that occurs in NSCLC patients. In addition, ZD6474 is thought to block the formation of new blood vessels, which may limit new blood vessel growth in the tumor and "starve" the tumor.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete physical exam, including measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will be asked questions about your ability to perform daily activities (performance status evaluation). You will have blood (about 2-3 teaspoons) drawn for routine tests. You may have up to 3 electrocardiograms (ECG --a test that measures the electrical activity of the heart). You will also have a chest x-ray and computed tomography (CT) scans of your chest to measure the status of the disease. You will be asked to fill out 2 questionnaires about the quality of your life and shortness of breath. The questionnaires will take about 10-15 minutes, total, to complete. Women who are able to have children must have a negative blood (about 1-2 teaspoons) pregnancy test.
If you are found to be eligible to participate in the study, you will have an indwelling intrapleural catheter placed. You will have to sign a separate consent document before placement of an indwelling intrapleural catheter can be performed. The pleural fluid will be collected at each clinic visit. The fluid will be saved and analyzed to answer research questions that are part of this study. You will also need to drain your pleural fluid everyday. The research nurse will provide you with instructions on how to drain your daily pleural fluid and a patient "diary" to take home to record the amount of fluid drained every day. The study doctor or research nurse will review the diary at each clinic visit.
After placement of the intrapleural catheter (Day 1), you will receive treatment with ZD6474. Treatment on this study is for 10 weeks. You will take a ZD6474 tablet by mouth each morning. The tablet should not be chewed, crushed, or divided, and should be taken with 8 ounces of water. You should take the tablet at about the same time every day.
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
- •Patients with pleural effusion requiring placement of an indwelling intrapleural denver catheter for recurrent symptomatic malignant pleural effusion
- •Pathologic documentation of NSCLC
- •Performance status 0 to 2 (Eastern Cooperative Oncology Group (ECOG) scale)
- •International Normalized Ratio (INR) </= 2.5
- •Signed informed consent prior to any study related procedures
- •Subject must be female or male age 18 years or over
排除标准
- •Chemotherapy or other anticancer therapy in the 3 weeks prior to study. Palliative radiotherapy will be allowed to extra thoracic sites 2 weeks prior to study
- •No other prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for at least two years
- •Laboratory results sustained at:Neutrophils less than 1.5x10^9/L or platelets less than 100x10^9/L; Serum bilirubin >1.5 x the upper limit of reference range (ULRR);Serum creatinine>1.5xULRR or CrCl </=30 mL/minute(calculated by Cockcroft-Gault formula). Potassium,<4.0 mmol despite supplementation;serum calcium (ionized or adjusted for albumin),or magnesium out of normal range despite supplementation;Alanine aminotransferase(ALT)or aspartate aminotransferase(AST) > 2.5 x ULRR or alkaline phosphatase(ALP)> 2.5 x ULRR,or > 5 x ULRR if judged by the investigator to be related to liver metastases
- •Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension or renal diseases
- •Diagnosis of post-obstructive pneumonia or other serious infection in the 14 days prior to registration
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- •Clinically significant cardiovascular event such as Myocardial infarction; New York Heart Association (NYHA) classification of heart disease >/=2 within 3 months before entry; or presence of cardiac disease that in the opinion of the Investigator increase the risk of ventricular arrhythmia
- •History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded
- •Previous history of corrected QT interval (QTc) prolongation with other medication that required discontinuation of that medication
- •Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age
- •QTc with Bazett's correction that is unmeasurable, or >/=480 msec on screening ECG. If a patient has QTc >/=480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study). Patients who are receiving a drug that has a risk of QTc prolongation are excluded if QTc is >/= 460 msec
- •Any concomitant medication that may cause QTc prolongation or induce Torsades de Pointes
- •Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
- •Women who are currently pregnant or breast feeding
- •Participation in a clinical trial of any investigational agents within 30 days prior to commencing study treatment
- •In 2nd line or later, the last dose of prior chemotherapy is discontinued less than 3 weeks before the start of study therapy
- •In 2nd line or later, the last radiation therapy discontinued less than 2 weeks before the start of study therapy except palliative radiotherapy
- •If it is in 2nd line or later, any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
- •Previous enrollment or randomization of treatment in the present study
- •Patients with pre-existing placement of intrapleural catheter
- •Presence of left bundle branch block (LBBB.)
- •Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
- •Patients may not have a history of a bleeding diathesis
- •Currently active diarrhea that may affect the ability of the patient to absorb the ZD6474 or tolerate diarrhea
- •Concomitant medications that are potent inducers (rifampicin, rifabutin, phenytoin, carbamazepine, phenobarbital and St. John's Wort) of CYP3A4 function
研究组 & 干预措施
ZD6474
300 mg/day orally for 10 weeks.
干预措施: ZD6474 (Drug)
结局指标
主要结局
Median Time to Pleurodesis
时间窗: Time from initiation of treatment and catheter insertion up to a maximum of 10 weeks
Time to pleurodesis from initiation of treatment to catheter removal as measure of pleural effusion Improvement (amount of pleural fluid drainage) where objective was to examine whether ZD6474 would help participants to improve the condition of pleural effusion, and thus remove the catheter earlier. Cox model analysis applied to examine the effect of covariates on the time to catheter removal.
次要结局
未报告次要终点