A Phase I Trial of Bevacizumab and Bortezomib in Patients With Advanced Malignancy
Bevacizumab is an anti-cancer drug designed to prevent or slow down the growth of cancer
cells by blocking blood vessels that supply nutrients necessary for tumor growth.
Bortezomib is an anti-cancer drug designed to block the proteins needed for tumor growth.
This may cause cancer cells to die.
If you are found to be eligible to take part in this study, you will be enrolled into a
group of about 6 participants. The first group of participants will receive the lowest dose
of bevacizumab and bortezomib combined. The next group of participants will receive the next
highest dose of bevacizumab and bortezomib combined. This process will continue until the
study doctor finds the highest dose that can be tolerated. The dose that you receive will
depend on when you are enrolled in this study and the safety data that is available at that
time. The dose of bevacizumab and bortezomib that you receive may be lowered if you do not
tolerate the study drug combination well. You will not receive any doses of the study drug
higher than the dose you are first assigned to.
Bevacizumab and bortezomib will be given in "cycles." Cycles will be about 21 days long or
longer, depending on any side effects you may experience. During Cycle 1, Day 1, you will
receive bevacizumab by vein over 90 minutes. If bevacizumab is well tolerated in Cycle 1, it
will given over 60 minutes in Cycle 2. If it is well tolerated in Cycle 2, it will be given
over 30 minutes in Cycle 3. It will continue to be given over 30 minutes in further cycles
as long as the drug is still being well tolerated. Depending on which dose level you are
assigned to, you will receive bortezomib on Days 1 and 8, or on Days 1, 4, 8, and 11. You
will receive bortezomib by vein over about 1-5 minutes.
You will have blood drawn (about 1 tablespoon each time) for routine tests once a week
during Cycle 1. You will have a physical exam sometime between Days 7 to 14 during Cycle 1.
During the rest of the cycles, you will have a physical exam and blood drawn (about 1
tablespoon each time) for routine tests once every 3 weeks. The status of the disease will
be measured by a CT or MRI scan after every 2 cycles.
Once the highest tolerable dose (maximum tolerated dose or MTD) of the combination of
bevacizumab and bortezomib is found, up to 15 additional participants with advanced cancer
will be enrolled to receive that dose, so that researchers can learn more about the effects
of the study drugs on the tumor. A tumor biopsy will be required within two weeks before
the first treatment and again at the end of the first cycle for those patients. Up to 10
additional patients with kidney cancer will be enrolled to receive the highest tolerable
dose. Tumor biopsies are optional for patients with kidney cancer.
You may continue to receive bevacizumab and bortezomib on this study, unless the cancer gets
worse or you experience any intolerable side effects.
Once your participation is over in this study, you will receive standard of care follow-up
for the disease.
This is an investigational study. Bevacizumab and bortezomib are both FDA approved and
commercially available. Bevacizumab is FDA approved for the treatment of colorectal cancer.
Bortezomib is FDA approved for the treatment of multiple myeloma. The combination use of
bevacizumab and bortezomib is investigational and authorized for use in research only.
Up to 111 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
Maximum tolerated dose (MTD) and Dose-limiting toxicities (DLT) of Combination Treatment with Bevacizumab and Bortezomib
The MTD is defined as the highest dose studied in which the incidence of DLT was less than 33%.
Weekly during 21 Day Cycle
Gerald Falchook, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|