An Open Label Phase I Trial of PBI-05204 in Advanced Cancer Patients
The Study Drug PBI-05204, made from the oleander plant, is designed to prevent the growth of
cancer cells by affecting proteins that lead to cell death.
Screening Tests
Before you can begin receiving the study drug, you will have "screening tests" to help the
doctor decide if you are eligible to take part in this study. The following tests will be
performed:
- You will have a physical exam, including measurement of vital signs (blood pressure,
heart rate, temperature, and breathing rate), height, and weight.
- You will be asked how well you are able to perform the normal activities of daily
living (performance status evaluation).
- Your complete medical history will be recorded.
- You will have an electrocardiogram (ECG -- a test that measures the electrical activity
of the heart).
- You may have an echocardiogram (a picture of your heart using sound waves), if
applicable.
- You will have a computed tomography (CT) scan or magnetic resonance imaging (MRI) to
check the status of the disease.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- Women who are able to have children must have a negative blood (about 2 teaspoons) or
urine pregnancy test.
Study Drug Dose Level:
If you are found to be eligible to take part in this study, the amount of PBI-05204 that you
take will be based on how many participants have been enrolled before you, and on the safety
information that is available. There may be up to 6 participants enrolled in each group. The
first group of participants enrolled on this study will receive PBI-05204 at the lowest dose
level. If no intolerable side effects are experienced, the next group of participants will
take a higher dose level. This process will continue until researchers find the highest
dose of PBI-05204 that can be given without intolerable side effects occurring.
Study Drug Administration:
Depending on which group you are enrolled in, you will take the PBI-05204 capsules by mouth
every day at the same time or twice a day (every 12 hours). Your Doctor will tell you which
schedule you are on. You will take the drug on Days 1-21. On Days 22-28 you will take no
study drug. Each 28 days is called a "study cycle".
Study Visits:
At the Predose Visit, 1-7 days before Day 1 of Cycle 1 you will have the following tests and
procedures performed:
- You will have a physical exam, including measurement of your vital signs, height, and
weight.
- You will have a performance status evaluation.
- Urine will be collected for routine tests.
- You will have an ECG, if applicable
- You will have your heart rate monitored by a Holter monitor. A Holter monitor is a
machine that continuously records the heart's rhythms. Electrodes (small conducting
patches) are stuck onto your chest and attached to a small recording monitor. You carry
the Holter monitor in a pocket or in a small pouch worn around your neck or waist. The
monitor is battery operated. After 24 hours, you return the monitor to the study
doctor. The study doctor will look at the records and see if there have been any
irregular heart rhythms.
- Blood (about 3-4 teaspoons) will be collected for routine tests.
- Women who are able to have children will have a blood (about 2 teaspoons) or urine
pregnancy test.
On Day 1 Cycle 1 you will have the following tests and procedures performed:
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- You will have an ECG. The ECG will be repeated on Day 1 of every later Cycle.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- You will take your dose of PBI-05204 by mouth.
- Blood (about 2 teaspoons each time) will be collected for PK testing before you take
the first daily dose of the study drug and then 1, 2, 4, 6, and 8 hours later.
- Blood (about 6 teaspoons) will be collected for pharmacodynamic (PD) testing before you
take the study drug. PD testing is used to look at how the level of study drug in your
body may affect the disease.
On Day 2 of Cycle 1 you will have the following:
- You will take your dose of PBI-05204 by mouth
- You will have an ECG.
On Day 7 of Cycle 1 you will have the following:
- Blood (about 6 teaspoons) will be drawn for PD testing.
- You will take your dose of PBI-05204 by mouth.
- You will have your heart rate monitored by a Holter monitor.
On Day 8 of Cycle 1 you will have the following tests and procedures performed:
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- You will take your dose of PBI-05204 by mouth.
- Blood (about 2 teaspoons each time) will be collected for PK testing before you take
the first daily dose of the study drug and then 1, 2, 4, 6, and 8 hours later.
Additional blood (about 2 teaspoons each time) will also be collected for PK testing
before you take the second daily dose of the study drug and then 1, 2, 4, and 12 hours
later.
- You will have an ECG.
On Day 15 of Cycle 1 you will have the following tests and procedures performed:
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- You will have an ECG.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- You will take your dose of PBI-05204 by mouth.
- Blood (about 2 teaspoons each time) will be collected for PK testing before you take
the first daily dose of the study drug and then 1, 2, 4, 6, and 8 hours later.
On Day 21 of Cycle 1 you will have the following tests and procedures performed:
- You will have a physical exam, including measurement of your vital signs.
- You will have a performance status evaluation.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- You will take your dose of PBI-05204 by mouth.
- Blood (about 2 teaspoons each time) will be collected for PK testing before you take
the first daily dose of the study drug and then 1, 2, 4, 6, and 8 hours later.
Additional blood (about 2 teaspoons each time) will also be collected for PK testing
before you take the second daily dose of the study drug and then 1, 2, 4, and 12 hours
later.
- Blood (about 6 teaspoons) will be collected for PD testing.
During the last week of Cycle 2, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs, height and
weight.
- You will have a performance status evaluation.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests.
- You will have a CT or MRI scan to check the status of the disease.
- Women who are able to have children will have a blood (about 2 teaspoons) or urine
pregnancy test.
On Day 1 of Cycles 3 and beyond you will have a physical exam, including measurement of your
vital signs.
At the end of every 2 cycles beginning with Cycle 4 (Cycles 4, 6, 8, and so on) blood (about
3-4 teaspoons) and urine will be collected for routine tests. You will have a CT or MRI.
If you are enrolled in the expansion group, blood (about 2 teaspoons each time) will be
collected for PK testing before you take the daily dose of the study drug and then 1, 2, 4,
6, 8 and 24 hours later on Day 1 of Cycle 1. On Days 8, 15 and 21 of Cycle 1, blood (about 2
teaspoons each time) will also be collected for PK testing before you take the daily dose of
the study drug and then 1, 2, 4, 6 and 8 hours later.
If you are enrolled in the expansion group, you will also have two mandatory tumor biopsies
collected within 1- 7 days before you take your daily dose of the study drug and once during
Days 15-21 of Cycle 1. To collect the biopsy, your doctor will insert a needle into the
tumor and withdraw a small piece of the tumor. The tumor tissue will be studied to look at
special "markers" in the tumor that may help researchers predict who may benefit from the
study drug.
Length of Study:
You will remain on study until the disease gets worse, you decide to come off study, your
doctor decides it is in your best interest to come off the study, you have intolerable side
effects, or the sponsor closes the study.
If you decided to leave the study early you must tell the study doctor in writing and return
any unused study drug. You must complete the end-of-study visit.
End-of-Study Visit:
Once you are off-study, you will have an end-of-study visit within 30 days after the last
dose of PBI-05204. At this visit, the following tests and procedures will be performed:
- You will have a physical exam, including a measurement of your vital signs.
- You will have a performance status evaluation.
- You will have an ECG.
- You will have your heart rate monitored by a Holter monitor.
- Blood (about 3-4 teaspoons) and urine will be collected for routine tests
- You will have a CT/MRI scan to assess your tumors.
- Women who are able to have children must have a blood (about 2 teaspoons) or urine
pregnancy test.
Long-Term Follow-up:
After you complete the end-of-study visit, your study doctor will continue to contact you or
your family doctor for a minimum of 30 days. You may be contacted by a phone call (less than
5 minutes), and you will be asked about your general health.
This is an investigational study. PBI-05204 is not FDA approved or commercially available.
At this time, PBI-05204 is only being used in research. Up to 52 patients will take part in
this study. All will be enrolled at M. D. Anderson.
Interventional
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Continuous assessment of safety throughout entire study period and determination of dose-limiting toxicities during and at the end of 28 Day Cycle(s).
Yes
David S. Hong, MD
Principal Investigator
M.D. Anderson Cancer Center
United States: Institutional Review Board
2007-0375
NCT00554268
October 2007
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |