Treatment of Malignant Pleural Effusion With ZD6474, a Novel Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor
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.
During your participation on this study, you will have a physical exam, routine blood tests
and chest x-ray at Weeks 2, 6, and 10. At Weeks 6 and 10, you will also have a CT scan.
You will have an ECG at Weeks 1, 2, 4, and 8. Your doctor may decide to have additional
ECGs to monitor your condition or if you experience a heart rate of less than 50 at any time
during study participation. You will also be asked to complete 2 questionnaires about the
quality of your life and any shortness of breath you are experiencing. You will complete
these questionnaires at home and return them to the research staff at each clinic visit. You
will be asked to record your weekly blood pressure for the first 6 weeks of study treatment.
The study doctor or research nurse will review the log at each clinic visit.
If you are benefitting from the study treatment and your doctor feels that it is your best
interest, you may continue to receive the study drug longer than 10 weeks. During your
participation in this extended treatment phase, every 4 weeks you will have a physical exam
and your performance status will be evaluated. You will have blood (about 2-3 teaspoons)
drawn for routine tests. Every 4 weeks, you will have ECGs performed. You will also have a
chest x-ray and computed tomography (CT) scans of your chest to measure the status of the
disease every 8 weeks. Your study drug will continue to be provided to you.
You may be taken off study early if you have intolerable side effects or the disease gets
worse.
This is an investigational study. ZD6474, the investigational drug to be used in this
study, is not approved by the FDA for commercial use; however, the FDA has permitted its use
in this research study. Up to 25 patients will take part in this study. All will be
enrolled at M. D. Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pleural Effusion Improvement (amount of pleural fluid drainage)
Time from initiation of the treatment, i.e., time of inserting Denver catheter, to the removal of Denver catheter
No
Carlos Jimenez, M.D.
Principal Investigator
M.D. Anderson Cancer Center
United States: Food and Drug Administration
2005-0929
NCT00402896
October 2006
October 2014
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |