Exploratory Study of Avastin (Bevacizumab) and RAD001 (Everolimus) in Advanced Low or Intermediate Grade Neuroendocrine Carcinoma (AVF3961s) (CRAD001C2481)
The Study Drugs:
Avastin is designed to prevent the formation of new blood vessels that help cancer cells to
grow. RAD001 is designed to block a protein that is important in the growth of cancer
If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to one of two treatment groups. During Cycle 1, one group will
receive Avastin and the other group will receive RAD001. Each study cycle is 3 weeks long.
In Cycle 2 and every cycle after that, participants in both groups will receive both study
drugs. There is an equal chance of being assigned to either group.
RAD001 tablets are taken once a day by mouth, followed by a large glass of water. The
tablets are in a blister-pack under aluminum foil. The blisters should only be opened at
the time you take the study drug.
You may either take RAD001 on an empty stomach or after a low-fat meal. Some examples of
low-fat meals include: cereal with fat-free milk, muffin or bagel with fat-free spread, or
fruit salad. You should avoid taking RAD001 after large fatty meals because this will lower
the amount of RAD001 your body absorbs. Your dietary habits around the time you take RAD001
should be as consistent as possible throughout the study.
You should take RAD001 at about the same time each day. The study staff will give you a
medication diary that you should bring to every study visit. You will be asked to use the
diary by writing down the date and time you take RAD001, how many tablets you take, and any
side effects you may experience.
Avastin is given through a needle in a vein in the arm. The first dose will be given over
about 90 minutes. If no intolerable side effects occur, the second dose will be given over
about 60 minutes, and if again no intolerable side effects occur, each dose after that will
be given over about 30 minutes.
If you experience side effects from an Avastin infusion (such as fever/chills), you may
receive additional medicine(s) at that time and before each later Avastin dose, in order to
decrease the risk of side effects.
On Day 1 of Cycle 1, you will receive your assigned study drug.
At the beginning of Cycle 2 and every cycle after that, you will be asked about any side
effects you are experiencing. You will have a complete physical exam performed, including
measurement of your vital signs and weight. Blood (about 3 teaspoons) and urine will also
be collected for routine tests.
On Day 8 of Cycles 1 and 2 only, about 2 teaspoons of blood will be drawn for routine tests.
These blood draws may be done at a local lab closer to your home.
Every 9 weeks, to check the status of the disease, you will have either CT scans or MRI
scans of the tumor(s). The scans will be the same type that you had performed during
screening. You will also have additional blood drawn (about 1-2 tablespoons each time) to
check any tumor markers that were found to be increased in your blood during the screening
In order to learn about the flow of blood to the tumor, non-routine functional CT scans will
be performed at the end of Cycles 1 and 3. When possible, these scans will be performed at
the same times as the routine CT scans.
Length of Study Treatment:
You may receive up to 12 cycles of study treatment, as long as you are benefitting. You
will be taken off study early if the disease gets worse or intolerable side effects occur.
This is an investigational study. RAD001 is not commercially available or FDA approved for
this type of cancer. Avastin is commercially available and FDA approved for the treatment
of advanced cancer of the colon and rectum. At this time, this drug combination is being
used for research only.
Up to 36 patients will be enrolled in this study. All will be enrolled at The University of
Texas (UT) MD Anderson Cancer Center.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Net Change Relative to Baseline in Tumor Blood Flow
Tumor blood flow (ml/min/100gm) determined by functional computed tomography (CT). Functional CT at baseline, after first and third cycles (21 day cycles). Change (percentage) calculated as tumor blood flow measured at baseline compared to tumor blood flow measurement taken at end of Cycle 1, week 3 (21 days), and again at end of Cycle 3, Week 9 (63 days).
Baseline to end of Cycle 3 (63 days)
James Yao, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|