Phase I/II Trial of Preoperative Radiotherapy With Concurrent Bevacizumab, Erlotinib and Capecitabine for Locally Advanced Rectal Cancer
The Study Drugs:
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels.
Erlotinib hydrochloride is designed to block the activity of a protein found on the surface
of many tumor cells that may control tumor growth and survival. This may stop tumors from
Capecitabine is designed to interfere with the growth of cancer cells.
The study has 2 parts, called Phase I and Phase II. In the Phase I portion, participants
will be treated with 1 of 4 dose combinations of capecitabine, bevacizumab, and erlotinib
hydrochloride, along with radiation therapy. The dose level of capecitabine and erlotinib
hydrochloride will change during Phase I, but the dose levels of bevacizumab and radiation
therapy is the same for all participants. The first group of participants will be given the
lowest dose combination. If that group does not experience intolerable side effects, the
next group of participants will be enrolled at a higher dose level. This will continue
until the highest tolerable dose level of the study drug and radiation therapy combination
is found (called the maximum tolerated dose, or MTD).
Based on the results of Phase I, researchers will decide the MTD level of chemotherapy and
radiation therapy. In Phase II, participants will be treated at the MTD dose level. Up to
26 participants will be treated in each phase.
Radiation and Chemotherapy Administration:
If you are found to be eligible to take part in this study, you will begin radiation
therapy. The radiation therapy will be given once a day for 5 days in a row (Monday-Friday)
each week, for up to 5 weeks and 3 days. You will have up to a total of 28 radiation
treatments. Each radiation treatment will take about 30 minutes.
You will take the chemotherapy drug capecitabine by mouth twice a day as a tablet on each of
the days that you receive radiation therapy. These pills will not be taken on Saturday and
Sunday. You must not be taking the drug cimetidine, and must be off of coumadin for at least
1 week and sorivudine and brivudine for at least 4 weeks before starting capecitabine and
during the entire capecitabine therapy. If you are not able to stop taking coumadin, you
will need extra blood tests performed throughout the study to check your bleeding and
You will receive the drug bevacizumab by vein once every 2 weeks for 6 weeks (a total of 3
doses). The infusion will at first last 90 minutes. If there are no allergic reactions,
fevers, or chills after the first infusion, the infusion time for the second dose will be
shortened to 60 minutes. If there is no allergic reactions or side effects during the
second drug infusion, the last infusion of bevacizumab will be given over 30 minutes. If
you do have some reactions to the infusion, you may receive extra preventive medications
before the infusion, and the length of time may need to stay at 90 minutes.
You will take the chemotherapy drug erlotinib hydrochloride by mouth as a tablet once a day.
Your doctor will tell you whether you will take erlotinib hydrochloride during the first 3
weeks of radiation therapy only, or during the whole time you are getting radiation therapy,
up to 6 weeks.
During the study, you will have the following tests performed:
- You will have physical exams once a week.
- Every week, blood (about 2 teaspoons) will be drawn for routine tests.
- You will have a routine urine test in the first and third week of radiation therapy.
- The possible development of side effects will be closely monitored during weekly visits
with your doctors.
At 6-8 weeks after you have stopped receiving radiotherapy, you will have a physical exam,
routine blood tests (about 2 teaspoons), and a urine test.
At least 8 weeks after you have stopped receiving radiotherapy, you will have the rectal
tumor removed by surgery. This is considered the standard of care and you will sign a
separate surgical consent document.
Length of Study:
You will receive radiation therapy with capecitabine, bevacizumab, and erlotinib
hydrochloride for 5 ½ to 6 weeks. At least 8 weeks after you stop receiving radiotherapy,
you will have surgery. You may then receive additional chemotherapy.
You may be taken off study if the disease gets worse or you experience intolerable side
After surgery and possible chemotherapy after surgery, you will be seen by a doctor every
3-4 months for 1 year, and then every 6 months for the next 3 years. You will have blood
tests at these doctor visits. You will also have CT scans within 4-6 months after
completion of chemotherapy then every 6 months for the first 3 years, and then once a year
for the next 2 years. These tests are all the standard of care procedures for treatment of
This is an investigational study. Capecitabine and bevacizumab have been approved by the
FDA for the treatment of metastatic colorectal cancer. Erlotinib hydrochloride has been
approved by the FDA for treatment of pancreatic cancer, but not for colorectal cancer. The
combination of capecitabine, erlotinib and bevacizumab with radiation therapy has not been
approved by the FDA. At this time, this combination is being used in research only. Up to
52 patients will take part in the 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
Maximal tolerated dose (MTD)
Continuoual Reassessment Weeks 1- 6
Prajnan Das, MD
M.D. Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|