A Phase I Trial of Sirolimus (mTOR Inhibitor) and Vorinostat (Histone Deacetylase Inhibitor) in Patients With Advanced Cancer
The Study Drugs:
Vorinostat is designed to prevent or slow down the growth of cancer cells by blocking
proteins.
Sirolimus is designed to block a protein called mTOR inside the cancer cell. This may
interfere with the growth or spread of cancer cells or possibly kill the cancer cells.
Study Drug Groups:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of sirolimus and vorinostat based on when you joined this study. Up to 9 dose levels
of sirolimus and vorinostat will be tested. Three (3) to 9 participants will be enrolled at
each dose level. The first group of participants will receive the lowest dose level of the
study drug combination. Each new group will receive a higher dose than the group before it,
if no intolerable side effects were seen. This will continue until the highest tolerable
dose of the combination of sirolimus and vorinostat is found.
Once the highest tolerated dose of the combination of sirolimus and vorinostat is found, up
to 14 participants with the tumor type that is most likely to respond to the study drug
combination will receive the study drugs at that dose level.
Study Drug Administration:
Each study "cycle" is 28 days.
Everyday, you will take sirolimus by mouth 1 time a day. You should take it at about the
same time each day with food and a cup (8 ounces) of water.
On Day 7 of Cycle 1, you will start taking vorinostat by mouth 1 time a day. You should take
it at about the same time each day with food and a cup (8 ounces) of water.
Once you start taking vorinostat, you will take both drugs everyday while you are on study,
unless told otherwise by your doctor.
Study Visits:
At every study visit, you will be asked about any current health conditions you have, drugs
you may be taking, and if you have had any side effects.
About Days 8 and 22 of Cycle 1:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
About Day 15 of Cycle 1, blood (about 2 teaspoons) will be drawn for routine tests.
About Day 22 of Cycles 2 and beyond:
- You will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests.
Every 4 weeks, you will have a blood (about 1 teaspoon) drawn or urine collected for a
pregnancy test if you are able to become pregnant.
Every 8 weeks, you will have an x-ray, CT scan, MRI, and/or PET/CT to check the status of
the disease. If the study doctor thinks it is needed, they will be performed more often.
Length of Study:
You may continue taking the study drugs for as long as you are benefitting. You will be
taken off study if you experience intolerable side effects, the study doctor thinks it is in
your best interest, or the disease gets worse.
This is an investigational study. Sirolimus is FDA approved and commercially available as
an anti-rejection drug for kidney transplant recipients. Vorinostat is FDA approved and
commercially available for the treatment of cutaneous T-cell lymphoma. The combination of
these drugs is investigational.
Up to 107 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)
Every 28 day cycle
Yes
Filip Janku, MD, PHD
Principal Investigator
UT MD Anderson Cancer Center
United States: Institutional Review Board
2009-0729
NCT01087554
March 2010
Name | Location |
---|---|
UT MD Anderson Cancer Center | Houston, Texas 77030 |