Phase I-II Study of Avastin®+ Bortezomib for Patients With Recurrent or Refractory Non-Squamous NSCLC
Bortezomib is designed to enter cells and interfere with a substance found inside cells that
is responsible for allowing cells to divide.
Avastin® is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.
If you are found to be eligible to take part in this study, depending on when you enroll,
you will be assigned to one of up to 4 treatment groups. There will be 3 participants in
each of the first few groups, and an additional 30 participants in the last group. The
first few (2 or 3) groups are part of the first phase of the study, and the last group (3rd
or 4th) is part of the second phase. All participants will receive the same dose level of
Avastin®. The amount of bortezomib you receive will depend on when you enroll in the study.
The exact dose of bortezomib that you receive will be based on your height and weight. In
the first phase of the study, groups of participants will be assigned to one of 2 bortezomib
dose levels. The first group will receive the highest dose. The next groups will receive
either that same dose level, or if intolerable side effects occurred, a lower dose level.
For the second part of the study, the last group will receive the highest dose level that
did not cause intolerable side effects in the other groups.
A cycle of treatment is 3 weeks (21 days). Bortezomib will be given once a week for the
first 2 weeks of each cycle. Avastin® will be given every 3 weeks. (On Day 1 of each
cycle, you will receive both bortezomib and Avastin®.)
Bortezomib will be injected through a needle in your vein. Each injection will last about
3-5 seconds. After receiving each dose of bortezomib, the clinic staff will check how well
you are tolerating the drug. During that time, you will be asked about any side effects you
may be experiencing. Your doctor may decrease or pause the dose of bortezomib if you
experience certain side effects.
Avastin® will be given as an infusion through a needle in your vein, over 90 minutes. If
you tolerate the 90-minute infusion well, the second infusion will be given over 60 minutes.
If you tolerate the 60-minute infusion well, all following infusions will be given over 30
minutes. If you do not tolerate the shorter infusion time, future infusion times will be
increased until a tolerable level is reached.
Every 3 weeks, you will have a physical exam, including measurement of vital signs and
weight. Blood (about 2 teaspoons) will be drawn for routine tests. You will have a
performance status evaluation. On Day 8 of each cycle of treatment, blood (about 2
teaspoons) will be drawn for routine tests. The level of protein in your urine will be
monitored at least every 6 weeks.
You may continue receiving study treatment for as long as the cancer responds to the
treatment or for up to 1 year. Your doctor may decide to take you off this study if you
experience intolerable side effects or your health gets worse.
After you have stopped taking the study treatment, you will have a physical exam, including
measurement of vital signs. Blood (about 2 teaspoons) will be drawn for routine tests. You
will have a performance status evaluation, chest x-ray, and a CT or MRI scan. On an
indefinite basis, the study nurse will contact you by telephone from time to time to see how
you are doing.
This is an investigational study. Bortezomib has been FDA approved and it is registered in
Europe for the treatment of multiple myeloma patients who have received at least one prior
therapy. Avastin® has been FDA approved for the treatment of metastatic colorectal cancer
and non-small cell lung cancer. However, bortezomib and Avastin® are not FDA-approved for
this type of cancer, and they have been authorized for use together in research only. Up to
42 patients will take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
MTD is defined as the highest dose level in which 6 patients have been treated with 2 patients with dose limiting toxicity (DLT).
Bonnie S. Glisson, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration