A Phase I Trial of Docetaxel and Sirolimus in Patients With Advanced Malignancies
The Study Drugs:
Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die.
It is believed to be weakly effective at killing blood vessels in tumor tissue as well.
Sirolimus is designed to block a protein called mTOR inside the cancer cell.
Prednisone is a corticosteroid that is similar to a natural hormone made by your body.
Prednisone is often given in combination with chemotherapy to treat cancer.
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of the combination of docetaxel and sirolimus based on when you joined this study. Up
to 12 dose levels of docetaxel and sirolimus will be tested. Three (3) to 6 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, if
no intolerable side effects were seen. This will continue until the highest tolerable dose
of docetaxel and sirolimus is found. Once the highest tolerable dose of docetaxel and
sirolimus is found, up to 12 more patients may be enrolled to further study the safety of
the drug at each of that dose.
If you have prostate cancer, you will also receive prednisone. All participants who receive
prednisone will receive the same dose level.
Study Drug Administration:
Each study cycle is 21 days.
Everyday, you will take sirolimus by mouth 1 time a day. Sirolimus can be taken with or
without food, but should be taken at the same time everyday.
On Day 1 of every cycle, you will receive docetaxel by vein over about 1 hour.
If you are taking prednisone, you will take it 2 times every day by mouth with food and
Every week for the first 3 weeks and then about every 3 weeks, blood (about 5 teaspoons)
will be drawn for routine tests. You will also have a physical exam.
Every 6 weeks, women who are able to have children will have blood drawn for a pregnancy
About every three weeks, blood (about 5 teaspoons) will be drawn for routine tests, to check
your kidney function, and for biomarker tests.
About every 6 weeks, you will have a CT scan and x-ray to check the status of the disease.
Length of Study:
You will be on study for as long as you are benefitting. You will be taken off the study if
the disease gets worse or you experience intolerable side effects.
If you experience intolerable side effects, you will be followed until the side effect has
resolved or the side effect does not continue to improve or get worse. The study doctor will
tell you what tests will need to be performed.
This is an investigational study. Docetaxel is FDA approved and commercially available for
the treatment of advanced cancers such as breast, lung, and prostate cancer. Sirolimus is
FDA approved and commercially available for the prevention of transplant rejection in kidney
transplant patients. Prednisone is FDA approved and commercially available for the
treatment of prostate cancer when given with docetaxel.
The combination of docetaxel and sirolimus, with or without prednisone, to treat advanced
cancer is investigational. Most patients in this study will receive docetaxel and sirolimus.
However, if you have prostate cancer, you will receive docetaxel, prednisone, and sirolimus.
Up to 68 patients will be enrolled 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
Maximum Tolerated Dose(MTDs) for Docetaxel - Sirolimus
Every week for first 3 weeks then every 3 weeks
Filip Janku, MD, PHD
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|