Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.
Temsirolimus is designed to block the growth of cancer cells, which may eventually cause the
cancer cells to die.
Carboplatin is designed to damage the DNA (the genetic material of cells)of cancer cells,
which may will eventually cause the cancer cells to die.
Paclitaxel is designed to damage the DNA of cancer cells, which may eventually cause the
cancer cells to die.
Sorafenib is designed to block the function of important proteins in cancer cells. These
proteins, when active, are in part responsible for the abnormal growth and behavior of
Study Drug Dose Level:
If you are found to be eligible to take part in this study, your doctor will decide which
study drugs you will receive based on the disease type and on the drugs you have taken in
Every participant will receive bevacizumab and temsirolimus. The study staff will tell you
which of the other 3 drugs (carboplatin, paclitaxel, or sorafenib) you will receive.
Once it is decided which drugs you will receive, you will be assigned to a dose level of
the drug combination based on when you join this study. Three (3) to 6 participants will be
enrolled at each dose level. The first group of participants on each drug combination will
receive the lowest doses. 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 each dose combination is found.
Your dose of study drugs may be lowered later, if you do not tolerate the study drug
Once the highest tolerated dose is found for each group, up to 10 more participants will be
added to each group at that dose level. This is called an extension group.
Study Drug Administration:
Each cycle is about 21 days or 28 days, depending on which study drug combination you
receive. If you experience side effects, the start of the next cycle may be delayed.
On Day 1 of each cycle, you will receive bevacizumab by vein. The first infusion is over 90
minutes. The next infusion may be over 60 minutes if the first infusion was
well-tolerated. If you tolerate the second infusion well, the third infusion may be over 30
On Days 1, 8, and 15 of each cycle, you will receive temsirolimus by vein. During Day 1 of
Cycle 1, you will receive it over 60 minutes. If you tolerate it well on Day 1 of Cycle 1,
it will be given over 30 minutes on Days 8 and 15 of Cycle 1 and over 30 minutes in further
cycles, as long you still tolerate it well.
If you are assigned to take carboplatin, you will receive it by vein over 1 hour on Day 1 of
If you are assigned to take paclitaxel on Dose Levels 1 - 8, 11-12, and 14, you will receive
it by vein over 3 hours on Day 1 of each cycle.
If you are assigned to take paclitaxel on Dose Levels 9, 10, 13, 15, 16, you will receive
paclitaxel by vein over 3 hours each week for 3 weeks. You will receive bevacizumab on
Days 1 and 15 of each cycle.Your doctor will tell you on which dose level you will be
If you are assigned to take sorafenib, you will take it by mouth 1 or 2 times every day (the
study staff will tell you how often to take it). You should take sorafenib on an empty
stomach, either 1 hour before a meal or 2 hours after a meal.
During Cycle 1:
- Urine will be collected for routine tests on Day 1.
- You will have a physical exam, including measurement of your weight and vital signs
(blood pressure, breathing rate, heart rate, and temperature).
- You will be asked how well you are able to perform the normal activities of daily
living (performance status) on Days 1 and 8.
- Blood (about 1 tablespoon) will be drawn for routine tests on Days 1, 8, and 15.
- If you are in the extension group, you will have a tumor biopsy for PK and biomarker
testing on Day 15.
On Day 1 of Cycles 2 and beyond:
- You will have a physical exam, including of your weight and vital signs..
- Your performance status will be recorded.
- Blood (about 1 tablespoon) and urine will be collected for routine tests
After Cycle 2, you will have a CT scan or MRI scan to check the status of the disease every
2-3 cycles. After 6 months, this may be performed up to every 4 cycles if the doctor thinks
it is in your best interest.
Length of Study:
You may remain on study for as long as the doctor thinks it is in you best interest. You
will be taken off study if the disease gets worse or intolerable side effects occur.
This is an investigational study. Bevacizumab, temsirolimus, carboplatin, paclitaxel, and
sorafenib are all commercially available. Bevacizumab is FDA approved for the treatment of
colorectal cancer and a type of lung cancer. Temsirolimus is FDA approved for the treatment
of kidney cancer that has spread. Carboplatin is FDA approved for the treatment of ovarian
cancer or non-small cell lung cancer. Paclitaxel is FDA approved for ovarian, breast
cancer, and AIDS-related Kaposi's sarcoma. It is also approved in combination with
cisplatin for the treatment of ovarian and non-small cell lung cancer. Sorafenib is FDA
approved for the treatment of kidney cancer.
The use of these drugs together is investigational.
Up to 278 patients will take part in this study. All will be enrolled at MD Anderson.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
MTD defined by dose-limiting toxicities (DLTs) that occur during the first four weeks of therapy.
Every 4 weeks
Shannon Westin, MD
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|