Phase 0 Trial Evaluating the Effect of Temsirolimus on Known Pharmacodynamic Targets
Temsirolimus is designed to block the growth of cancer cells, which may cause the cancer
cells to die.
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive temsirolimus by
vein over about 60 minutes on Day 1.
You will be assigned to a dose level of temsirolimus based on when you join this study. Up
to 5 dose levels of temsirolimus will be tested. Up to 3 participants will be enrolled at
each dose level. The first group of participants will receive the lowest dose level. Each
new group will receive a higher dose than the group before it, until the drug is found to
affect the enzyme that was tested for at screening.
At each study visit, you will be asked about any drugs you may be taking and about any side
effects you may be having.
On Day 1:
-Blood (about 2 teaspoons each time) will be drawn before you receive the study drug and 5
times over the 24 hours after you receive the study drug for pharmacokinetic (PK) testing.
PK testing measures the amount of study drug in the body at different time points.
Blood (about 4 teaspoons each time) will be drawn for pharmacodynamic (PD) testing. PD
testing measures how the level of study drug in your body may affect the disease. This
blood will be drawn at 1 or more of the following times, but if the doctor thinks it is
needed, blood will be drawn at 2 or all 3 of the following times:
- At 4 hours (+/- 2 hours) after the dose
- At 24 hours (+/- 3 hours) after the dose
- At 72 hours (+/- 24 hours) after the dose
After the blood for PD testing has been tested and the tests show that the study drug may be
causing changes to the tumor cells in at least 2 out of 3 participants, future participants
will have tumor tissue collected before and after dosing for testing. Leftover tissue from
an earlier biopsy can be used instead of a fresh biopsy before dosing, if it is available.
Length of Study:
You will be on study for up to 4 days. You will be taken off study early if you have
intolerable side effects.
Because it takes 4 days for temsirolimus to be completely processed by the body, you will
not be able to begin receiving drugs in any other study until 4 days after the dose.
This is an investigational study. Temsirolimus is FDA approved and commercially available
for the treatment of advanced renal cancer. Its use in other types of cancer is
Up to 30 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Participants' Pharmacodynamic (PD) Responses
PD response, significant S6 Kinase 1 (S6K1) inhibition, is defined at both the patient level and the dose level, 1) as compared with baseline, at least 50% reductions of S6K1 after treatment (biological criterion); 2) differences in log transformed S6K1 activity between post-treatment and baseline should be greater than threshold of 1.8 times standard deviation (SD) of baseline, which yields a 90% statistical confidence that it is not due to chance variation (statistical criterion).
Blood drawn at 4 hours (+/- 2 hours) after study drug
Daniel Karp, MD
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|