A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis
RTA 744 is designed to enter the spinal fluid and kill cancer cells both in the spinal fluid
and in the rest of body.
Before you can start receiving the study drug, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. Your complete
medical history will be recorded. You will be asked about any drugs you have taken and are
taking. You will have a physical exam, including measurement of vital signs (blood
pressure, heart rate, temperature, and breathing rate). You will have a neurological exam.
Blood (about 2 tablespoons) will be drawn for routine tests. This routine blood draw will
include a pregnancy test for women who are able to have children. To be eligible to take
part in this study, the pregnancy test must be negative. Urine will be collected over a
24-hour period to test kidney function and for routine tests. You will have a magnetic
resonance imaging (MRI) scan of the brain and spine.
You will have a chest x-ray. You will be asked questions about your ability to perform
daily activities (performance status evaluation). You will have an electrocardiogram (ECG
-- a test that measures the electrical activity of the heart). You will have either a
multiple gated acquisition scan (MUGA) or an echocardiogram to check your heart's health.
Samples (1 1/2 teaspoons) of cerebrospinal fluid from your spine and brain will be
collected to look for the presence of cancer cells. The spinal sample will be collected
through a lumbar puncture (spinal tap). The other sample will be taken from your brain
through an Ommaya Reservoir tap. Radioactive dye will be injected into the CSF to make sure
the CSF flows freely throughout the spinal canal. This is called an Indium-111 DPTA or
Technetium 99m-DPTA Flow Study.
If you are found to be eligible to take part in this study, you should receive the same dose
of RTA 744 throughout the study. The amount of study drug you receive will be determined by
when you begin the study. Every 21 days on study is considered 1 study "cycle." If you
have intolerable side effects, the drug dosing for the next cycle may be delayed for up to
21 days to allow any symptoms or side effects to resolve. You may be given a lower dose
level.
The first participant on this study will receive the dose that has been found to be
well-tolerated in an ongoing study involving participants with primary brain tumors. After
this participant has completed 1 study cycle, the next participant will be given a higher
dose of RTA 744. Each new participant will receive a higher dose level until a patient has
an intolerable side effect. When this happens, at least 2 more participants will be given
the dose level that causes the intolerable side effect. If there are no further intolerable
side effects to RTA 744, the next group of 3 participants will be given the next higher dose
of RTA 744. Each time, the dose of RTA 744 will not be increased until the effects of the
previous dose level have been studied. Doses will increase with each group of patients
until the highest tolerable dose is found.
On Day 1 Cycle 1, before you receive the first dose of RTA 744, you will have a physical
exam, neurological exam, and a performance status evaluation. If the screening neurological
exam was performed less than 1 week before Day 1, the neurological exam will not need to be
repeated. You will also be asked about any drugs, treatments, or herbal medicines you are
taking. You will be asked how you are feeling and if whether you are experiencing any
symptoms or side effects. Blood (less than 2 tablespoons) and urine will be collected for
routine tests, unless blood and urine were collected for screening within the past 72 hours.
After completion of these tests, you will receive RTA 744 through a needle in your vein
over a 2-hour period on Days 1-3. You must remain in the clinic for 2 hours after the drug
is given to make sure you are not having any side effects.
During Cycle 1, you will be asked to return to the clinic once a week for 3 weeks. At
these visits, blood (less than 2 tablespoons) will be drawn for routine tests. You will be
asked how you are feeling and whether you are having any side effects.
On Day 21, you will have a neurologic exam.
Before receiving the study drug on Day 1 of Cycles 2-18, you will have a physical exam,
neurological exam, and a performance status evaluation. You will also be asked about any
drugs, treatments, or herbal medicines you are taking. Blood (less than 2 tablespoons) and
urine will be collected for routine tests. You will have an ECG. Before Cycles 4, 6, 8,
10, 12, 14,16, and 18, you will have a MUGA scan or an echocardiogram. Once you have
completed the tests, you will receive the study drug in the same manner as Cycle 1.
During Days 1-3, you will be asked how you are feeling and to report any symptoms or side
effects you may have noticed during or after receiving RTA 744.
On Day 15, blood (about 3 teaspoons) will be drawn for routine tests. This blood draw may
be performed by an outside laboratory. If no clinic visit is scheduled on Day 15, you will
be contacted by telephone to find out if you have experienced any side effects. This phone
call should last less than 5 minutes.
On Day 21, blood (less than 2 tablespoons) will be drawn for routine tests.
One time (per cycle) between Day 15 and Day 21 of Cycles 2, 4, 6, 8, 10, 12, 14, 16, and 18,
a sample (about 2 teaspoon each time) of CSF will be collected from your spine through a
spinal tap, and from your brain through an Ommaya Reservoir tap. This will be done in order
to look for cancer cells. You will also have an MRI of the brain and spine.
An ECG will be performed during the last week of all cycles. A MUGA scan or an
echocardiogram will be performed during the last week of Cycles 4, 6, 8, 10, 12, 14, 16, and
18.
You will have an MRI within 1 week of the end of the last cycle.
You may remain on study for up to 18 cycles (13 months). You will be taken off study if the
disease gets worse or intolerable side effects occur.
Once you are off study, you will have an end-of-study visit. At this visit, your complete
medical history will be recorded. You will be asked about any drugs you have taken and are
taking. You will have a physical exam, including measurement of vital signs. You will have
a neurological exam. Blood (about 2 tablespoons) will be drawn for routine tests. Urine
will be collected over a 24-hour period to test kidney function and for routine tests. You
will have an MRI of the brain and spine.
You will have a chest x-ray. You will have a performance status evaluation. You will have
ECG and MUGA scans or echocardiogram. Samples (1 1/2 teaspoons each) of cerebrospinal fluid
from your spine and brain will be collected to look for the presence of cancer cells. The
spinal sample will be collected through a spinal tap. The other sample will be taken from
your brain through an Ommaya Reservoir tap. Radioactive dye will also be injected into the
CSF to make sure the CSF flows freely throughout the spinal canal.
THIS IS AN INVESTIGATIONAL STUDY. RTA 744 is not FDA approved or commercially available.
It has been authorized for use in research only.
Up to 18 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To study the highest tolerable dose of RTA 744 that can be given to patients with cancer that has spread to the meninges of the brain or the spine.
3 Years
Yes
Morris D. Groves, MD
Principal Investigator
M.D. Anderson Cancer Center
United States: Food and Drug Administration
2006-0506
NCT00512460
September 2006
March 2010
Name | Location |
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U.T.M.D. Anderson Cancer Center | Houston, Texas 77030 |