A Phase II Study of ZD6474 Alone and With Chemotherapy in Advanced NSCLC
ZD6474 is a new investigational drug that is thought to block the formation of new blood
vessels. The growth of new blood vessels is called angiogenesis. Angiogenesis is thought to
be essential for the growth of tumors beyond a small size. It is hoped that ZD6474 will
limit new blood vessel growth in the tumor and "starve" the tumor by limiting blood flow to
it. The second part of this study also includes paclitaxel (Taxol) and carboplatin
(Paraplatin). Both paclitaxel and carboplatin are standard chemotherapy drugs that are
approved by the FDA for use in the treatment of lung cancer.
Before beginning treatment on this study, you will have a biopsy of your tumor. The tissue
taken during this biopsy will be compared with the tissue taken after you receive ZD6474.
The tumor samples will be compared to see what effect ZD6474 has had on tumor cell death.
During the biopsy procedure, you will receive either a local or general anesthetic depending
on the location of your tumor and a small piece of tumor will be removed with a large
Before treatment starts, you will have a complete physical exam by a physician. You will
have routine blood (about 4 teaspoons) and urine tests. Women who are able to have children
must have a negative blood pregnancy test. You will have a chest x-ray and a CT or MRI
scan, a functional MRI, a bone scan if your doctor thinks it is necessary, and a brain scan.
You will also have an ECG (test to measure the electrical activity of the heart) and a ECHO
scan to make sure your heart is healthy enough to receive this treatment.
Treatment on this study will be given in 3-week cycles. During the first three cycles
(i.e., the first 9 weeks) you will take a ZD6474 tablet by mouth each morning on an empty
stomach. While on this study you will receive a physical exam every week. You will also
receive weekly blood tests (about 4 teaspoons) for the first 4 weeks of treatment. After
that you will receive blood tests (about 4 teaspoons) before every 3-week cycle.
After 2 weeks of treatment you will have another biopsy of your tumor, and another
functional MRI. After every 9 weeks of treatment and every 2 cycles thereafter you will
have a repeat CT or MRI to evaluate your tumor. If your disease has responded to ZD6474 or
stayed the same, you will go on to the second part of this study. If your disease has
gotten worse or intolerable side effects occur, you will be taken off this study and your
doctor will discuss treatment options with you.
If you continue on to the second part of this study, you will be randomly assigned (as in
the toss of a coin) to receive either: a) daily ZD6474 alone, or b) paclitaxel and
carboplatin every 3 weeks along with daily ZD6474. You have an equal chance of being
assigned to either group. If you receive paclitaxel, you will receive it as a 3-hour
infusion into a vein on the first day of each treatment cycle. If you receive carboplatin,
you will receive it by vein immediately following the paclitaxel infusion. The carboplatin
infusion will take between 15 and 30 minutes. Treatment with either daily ZD6474 or ZD6474
plus paclitaxel and carboplatin will continue until your diseases worsens or until severe
side effects occur.
This is an investigational study. ZD6474 is an investigational drug that has been approved
by the FDA for research use only. A total of up to 120 patients will take part in this
study. All will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Radiologic evaluations performed after weeks 2 and 9 of treatment, then every 2 cycles or as indicated if progressive disease is suspected.
Vassiliki Papadimitrakopoulou, M.D.
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|University of Texas M.D.Anderson Cancer Center||Houston, Texas 77030|