Phase I/II Study of ZD6474 in Patients With Recurrent High-Grade or Progressive Low-Grade Gliomas
Protocol # 06-C-0063
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the study outline?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Why is this trial important?
Malignant gliomas are the most common type of brain tumor in adults. It is estimated that each year there are approximately 12,000 new cases in the United States. Despite optimal treatment with surgery, radiation therapy, and chemotherapy, the prognosis remains poor. Once patients develop tumor progression, conventional chemotherapy is generally ineffective. Several reasons account for this poor response to chemotherapy including reduced drug delivery as a result of the blood-brain barrier, intrinsic resistance to most standard cytotoxic agents, tumor hypoxia, and a relatively low growth fraction. There is a need for more effective therapies based on novel mechanisms of action.
Who is eligible for this trial? (PDQ)
- Histologically proven primary malignant high-grade* glioma, including the following types:
- Glioblastoma multiforme
- Gliosarcoma
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Malignant glioma/astrocytoma not otherwise specified (NOS)
- Failed prior radiation therapy
- WBC ≥ 3,000/mm3, absolute neutrophil count ≥ 1,500/mm3, platelet count ≥ 100,000/mm3, hemoglobin ≥ 10 g/dL (transfusion allowed)
- SGOT and bilirubin ≤ 2 times upper limit of normal
- Creatinine ≤ 1.5 mg/dL and/or creatinine clearance ≥ 60 mL/min
- No active or serious cardiac disease
- No significant active hepatic, renal, or psychiatric diseases
- No hypertension not controlled by medical therapy
- No concurrent steroids OR on a stable dose of steroids for ≥ 5 days before study entry
- No other severe or uncontrolled systemic disease that would preclude study participation
* Progressive low-grade gliomas or infiltrative brain stem gliomas diagnosed by radiography, instead of biopsy, are allowed in the phase I portion of the study only.
What types of drugs or therapies are being used?
ZD6474 is an antitumor given orally.
What is the study outline? (PDQ)
This is a phase I, dose-escalation study followed by a phase II study. Patients are stratified according to current use of enzyme-inducing anti-epileptic drugs (yes vs. no).
Phase I
- Patients receive oral ZD6474 once daily on days 1-28
- Treatment repeats every 28 days for approximately 1 year in the absence of disease progression or unacceptable toxicity
- Groups of 3-6 patients receive escalating doses of ZD6474 until the maximum tolerated dose (MTD) is determined
Phase II
- Patients receive ZD6474 as in phase I at an established dose
What is the frequency and duration of the visits?
Treatment will consist of taking ZD6474 every day (in the morning) for 4 weeks or 1 cycle (each 4-week period is called a cycle). History and physical and neurological examinations will be repeated every 2 weeks for the first 4-week cycle and every 4 weeks thereafter. Participants will have a repeat head MRI scan every 4 weeks, prior to each cycle, and routine lab tests every 2 weeks throughout the study. Participants will have ECGs (electrocardiograms) done weekly for the first 8 weeks (2 cycles) and then every 4 weeks. On day 28 (+/- 3 days) of Cycle 1 only, participants will be asked to have additional blood tests drawn for measurement of the level of ZD6474 in their blood (pharmacokinetics).
Each visit to the clinical center will be 1-2 days in duration.
What are the costs?
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Who is the Principal Investigator?
Dr. Howard A. Fine is currently chief of the Neuro-Oncology Branch at NCI's Center for Cancer Research, and of the National Institute of Neurologic Disorders and Stroke. He received his B.A. from the University of Pennsylvania, Philadelphia, and his M.D. from Mount Sinai School of Medicine, New York. Dr. Fine completed both his internship and his residency in internal medicine at the Hospital of The University of Pennsylvania. Three years later he completed his fellowship in medical oncology at Harvard Medical School's Dana-Farber Cancer Institute, Boston, Mass. Before joining the NIH in 2000, Dr. Fine was both director of the Neuro-Oncology Disease Center at the Dana-Farber Cancer Institute, and of the Neuro-Oncology Program at the Harvard Cancer Center. This NCI senior investigator serves on several committees, including the Brain Tumor Program Review Group and the American Joint Committee on Cancer. Dr. Fine also serves on the editorial boards of several journals, including the Journal of Clinical Oncology, Neuro-Oncology, and The Oncologist. He has received several distinguished awards, including the Dana-Farber Harvard Cancer Center's Clinical Investigator Award in 1999, the Emil Frei III Clinical Investigator Award in 1993, and the Brain Tumor Society Research Award in 1992. His research interests include tumor angiogenesis, therapeutic gene transfer, and neural stem cell biology.
Where is this trial taking place?
NIH Clinical Center
National Institutes of Health
NCI Neuro-Oncology
10 Center Drive
Bethesda, Maryland 20892
Who are the contacts for this trial?
Howard A. Fine, M.D.
Principal Investigator
Phone: (301) 402-6298
Referrals:
Charisse Garcia, R.N.
Research Nurse
Phone: 301-402-6298
Fax: 301-480-2246
Toll free: 866-251-9686
garciacr@mail.nih.gov
Julie Peretti, R.N.
Research Nurse
Phone: 301-402-6298
Fax: 301-480-2246
Toll free: 866-251-9686
jperetti@mail.nih.gov
Tracy Cropper, R.N.
Research Nurse
Phone: 301-496-8250
Fax: 301-480-2246
Toll free: 866-251-9686
tcropper@mail.nih.gov
Where can additional information be found?
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