A Phase I Dose Escalation Study of Vandetanib (ZACTIMA, ZD6474) With Hypofractionated Stereotactic Radiotherapy in Patients With Recurrent Malignant Gliomas
Screening Prior to receiving any treatment, tests will be performed to determine overall
medical condition. This will include blood tests, questions about medical history, and
physical and neurological exams.
MRI scan of the brain, electrocardiogram (ECG) and chest X-ray will be performed as baseline
studies if they have not been performed in the last 28 days.
Women of child-bearing potential will also have a serum pregnancy test within 2 days before
taking the study drug.
During treatment If all of the study criteria are met and subject is enrolled in the study,
you will start taking the study drug at least 7 days before radiation therapy. You will take
the study drug once a day by mouth. You should take the study drug at about the same time
each day. If you forget to take a dose, take the missed dose as soon as you remember, as
long as it is at least 12 hours before the next dose is due. If it is less than 12 hours
until the next dose, do not take the dose you have missed. If you throw up within 30
minutes after you take the study drug, you should take another dose, and use medicine to
stop or relieve your vomiting per your doctor's instruction. You will continue to take the
study drug for a total duration of one year. The study will be stopped if your disease
progresses or there is excessive toxicity. Your participation in the study will be for one
year. However, we will continue to follow your disease status, general health and possible
treatment-related side effects after one year and for as long as possible.
This is a Phase I study. These types of studies usually include a small number of subjects
and are often called dose-escalation studies. Subjects in the first dose group will be
receiving a small dose of the study drug. If no unacceptable side effects are observed in
these subjects, the next group of subjects will receive the next higher dose of study drug.
The study drug doses planned are as follows:
Dose Level Drug dose Level 1 100 mg once a day Level 2 200 mg once a day Level 3 300 mg once
You will be assigned to one of three levels depending on when you enter the study.
You will also receive radiation therapy. The radiation dose is the same for all patients.
Radiation therapy will begin at least 7 days after you begin taking the study drug. The
radiation therapy will be once a day for 3 consecutive days. A special plastic mask will be
made for you and used to hold your head still during each radiation treatment.
Tests and procedures will be performed throughout your treatment to determine how your
cancer is responding and to monitor you for safety purposes. The tests and procedures will
be scheduled for you. The following tests and procedures will be performed:
- Physical examination, neurological examination, and ECG, right before, and in the
first, second, fourth, eighth and twelfth week of drug treatment; then once every three
- Brain MRI and quality of life questionnaires at one month and three month after
radiation therapy, then once every three months.
- Chest X-ray as your doctor determines.
Follow-up You will also have follow-up visits with your doctor once a month for the first 6
months, then once every three months. You may also see your doctor anytime as needed.
Duration You will be on this study for up to 12 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3.
Changhu Chen, MD
University of Colorado, Denver
United States: Food and Drug Administration
|University of Colorado Health Science Center||Aurora, Colorado 80010-0510|