A Phase I Study of Triciribine Phosphate Monohydrate (TCN-PM, VD-0002) in Adult Patients With Advanced Hematologic Malignancies
Triciribine is designed to prevent development of certain proteins which participate in the
abnormal growth of cancer cells.
Before you can start treatment on this study, you will have "baseline tests." These tests
will help the doctor decide if you are eligible to take part in the study. You will have a
physical exam, including measurement of vital signs (blood pressure, heart rate,
temperature, and breathing rate). Your complete medical history will be recorded. You will
be asked about your ability to perform everyday activities. You will have blood (about 4
teaspoons) and urine collected for routine tests. You will have an electrocardiogram (ECG
- a test to measure the electrical activity of the heart). Women who are able to have
children must have a negative blood (about 1 teaspoon) or urine pregnancy test.
You will also have a bone marrow aspiration and/or biopsy performed during the baseline
testing. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is
numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a
Certain patients who are at risk for involvement of disease in their central nervous system
may be required to have a lumbar puncture (spinal tap) done. A lumbar puncture involves
inserting a needle between the vertebrae of the back and then removing a small amount of
spinal fluid. The fluid will be checked for diseased cells, used to measure the level of
study drug in the fluid, and used to measure the level of a substance that shows how the
study drug is being handled by your body.
If you are found to be eligible for this study, you will start receiving Triciribine through
a needle in a vein, over about 1 hour, on Days 1, 8, and 15 of each 28-day study "cycle."
On each day you receive Triciribine, your vital signs will be measured before the start of
the infusion, at 30 minutes (half-way through the infusion), at the end of the infusion, and
at 1 hour after completing the infusion. An ECG will be done at the end of the infusion on
Day 1 of the first cycle only.
The amount of Triciribine you receive in each infusion will depend on when you enter the
study. At least 3 participants will be enrolled at each dose level. Each new group of
participants will receive a higher dose level than the group before, unless a level is
reached where the side effects are considered intolerable. This will help researchers to
find out the highest tolerable dose of Triciribine.
During the study, researchers will be checking the status of the cancer to see how it is
responding to the study drug. You will be checked once a week, or more often, depending on
how you are doing and according to your blood cell counts. Each check-up includes
measurement of your vital signs and blood (about 4 teaspoons) drawn for routine tests. You
will be asked about any side effects you may have experienced and any medications you are
During Cycle 1, you will have blood samples (about 1 teaspoon each time) drawn to measure
the amount of study drug in your blood at different times. This is called pharmacokinetic
(PK) testing. During Cycle 1, you will have a blood sample drawn before receiving the first
dose of Triciribine, and then 2, 24, 48, 72 ,and 96 hours after the Day 1 Triciribine dose.
If your doctor decides that it is necessary, an additional blood sample will also be drawn
between 120 and 144 hours (about 5-6 days) after your Day 1 dose of Triciribine. During
Cycle 1, you may also have blood samples (about 1 teaspoon) drawn to measure the action of
the study drug in the tumor cells. This is called pharmacodynamic studies (this defines how
the drug works on the tumor cells). During Cycle 1, you will have a blood sample drawn
(about 1 teaspoon) before receiving the first dose of triciribine and then 2 and 24 hours
after the Day 1 triciribine dose.
Before receiving each additional cycle, you will have a physical exam, including vital
signs. Blood (about 4 teaspoons) will be drawn for routine tests, and urine will be
collected. You will be asked about your ability to perform everyday activities. You will
have a bone marrow exam (including aspiration and/or biopsy) about every 28 days, in order
to check your response.
Certain participants who are at risk for involvement of disease in their central nervous
system may be required to have repeat lumbar punctures (spinal taps) performed once a week.
You may move to a higher dose level after your first cycle of therapy, if that increased
dose level is considered safe and the disease is stable or responding to treatment. If,
however, you experience serious side effects from the therapy, the doctor may decide to hold
any further therapy with Triciribine until those side effects go away, or may decide to stop
therapy altogether, if the side effects are intolerable. Depending on how fast the side
effects go away, you may be able to re-start your Triciribine infusions at a lower dose.
You may continue to receive Triciribine on study with no limit to the number of cycles that
you can receive, as long as your doctor finds that you are benefiting from this therapy and
you are not experiencing intolerable side effects. On the other hand, you may stop receiving
the study drug and be taken off study if it is not effective for you and/or the disease gets
worse, you develop another illness that interferes with the ability to safely give you the
study drug, or you are unable to tolerate the study drug.
If you leave the study for any reason, you will be asked to return for a follow-up visit at
the end of therapy (and possibly 30 days after your last dose of Triciribine, if you are not
receiving another type of treatment). A physical exam will be performed, and blood (about 2
teaspoons) will be drawn for routine tests, during both of these visits. If you have side
effects that are possibly related to the treatment, you may need to have more follow-up
visits. Blood (up to 3 tablespoons) may need to be drawn for routine tests at that time.
THIS IS AN INVESTIGATIONAL STUDY. Triciribine has been authorized by the FDA for use in
research only. Up to 34 patients will take part in this multicenter study. Up to 30
patients will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD) of TCN-PM (Triciribine)
The MTD is the highest dose level in which <2 patients of 6 develop first cycle dose-limiting toxicity (DLT). Evaluations after each dose level (28 day cycle).
28 day cycle
Farhad Ravandi-Kashani, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center||Tampa, Florida 33612|
|UT MD Anderson Cancer Center||Houston, Texas 77030|