Dose Escalation Study of Vandetanib With Hypofractionated Stereotactic Radiotherapy in Recurrent Malignant Gliomas (IRUSZACT0073)
The purpose of the study is to find out the highest dose of vandetanib that can be safely given with repeat radiation therapy.
This study drug has been designed to block certain chemical pathways that stimulate tumor to grow. The study drug has been shown to slow the growth of a number of types of cancers.
This will be a dose escalation study. A dose escalation study means that successive groups of patients will receive higher doses of the study drug. There are three dose levels. The dose of the study drug received will depend on the stage the study has reached at the time a patient decides to participate.
In addition to taking the study drug patients will also receive radiation therapy to the brain tumor for 3 days.
Hypothesis The objective of this study is to determine the maximally tolerated dose (MTD) of VANDETANIB given with 36 Gy hypofractionated stereotactic radiotherapy. The MTD will be dose of VANDETANIB at which no patients develop acute grade 5 toxicity and less than 30% of patients develop acute (within 30 days of radiation therapy) or delayed (at least 30 days after radiation completed) dose limiting toxicities.
Radiation: Fractionated Stereotactic Radiotherapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Dose Escalation Study of Vandetanib (ZACTIMA, ZD6474) With Hypofractionated Stereotactic Radiotherapy in Patients With Recurrent Malignant Gliomas|
- Incidence of acute and delayed ≥ grade 3 Central nervous system (CNS) toxicity by Common Terminology Criteria (CTC) v.3. [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
- Incidence of acute and delayed ≥ grade 3 non-CNS toxicity [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
- Progression-free survival at 6 months [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
- Overall survival [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
- Objective response rate [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
- Quality of survival [ Time Frame: 12 months. ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2007|
|Study Completion Date:||January 2011|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
Dose level 1:100 mg qd, 2:200 mg qd, 3:300 mg qd. Fractionated Stereotactic Radiotherapy: all patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.
Dose level 1:100 mg qd Dose level 2:200 mg qd Dose level 3:300 mg qd
Other Name: ZD6474, ZactimaRadiation: Fractionated Stereotactic Radiotherapy
All patients will receive 36 Gy of radiation in three fractions, given in three consecutive days.
Hide Detailed Description
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 a day
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 months.
- 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.
|United States, Colorado|
|University of Colorado Health Science Center|
|Aurora, Colorado, United States, 80045|
|Principal Investigator:||Changhu Chen, MD||University of Colorado Health Science Center|