Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2-Nonoverexpressing Metastatic Breast Cancers
Cetuximab is able to target a protein called the EGFR. EGFR is found on the surface of some
cells and plays a role in controlling cell growth. Cetuximab is designed to interfere with
the growth of cancer cells by binding to EGFR so that the normal (natural) epidermal growth
factors cannot bind and cause the cells to grow.
Carboplatin is designed to interfere with the growth of cancer cells by stopping cell
division. This may cause the cells to die.
Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. Your complete
medical history will be recorded. You will have a physical exam, including measurement of
your height and weight. You will have a performance status evaluation that will include
you being asked questions about your ability to perform daily activities. Blood (about 3
tablespoons) will be drawn for routine tests. Women who are able to have children must have
a negative blood (about 1 tablespoon) pregnancy test.
You will have a computed tomography (CT) scan, x-ray, bone scan, magnetic resonance imaging
(MRI) or positron emission tomography (PET) scan to measure your disease. These tests may
not need to be repeated if you have had them within 4 weeks before the screening visit.
Blood (about 5 tablespoons) will be drawn to look for tumor cells that may be circulating in
your blood and to run tests (genetic tests) to look at different genes that may have an
effect on your body's response to treatment.
In addition, if available, tumor tissue (leftover tumor tissue) from your breast cancer
surgery or biopsy will be obtained from your hospital and used to confirm your HER-2
negative status and to look at proteins that affect EGFR.
If you are found to be eligible to take part in this study, you will be assigned to Group B.
On Group B, you will receive cetuximab plus carboplatin. Group A (Cetuximab alone) has been
If you have been participating in this study since it started, you were randomly assigned,
like the flipping of a coin to one of two groups. If you were assigned to Group A, you
received cetuximab through a needle in your vein once every week. The first dose of
cetuximab was given over 2 hours, and the weekly maintenance dose was given over 1 hour. If
your disease got worse, you received carboplatin in addition to cetuximab. Both drugs were
given through a needle in your vein once every week for 3 weeks, followed by one dose of
cetuximab on week 4. Every 4 weeks was considered 1 study "cycle." If you were assigned to
Group B, you received cetuximab and carboplatin through a needle in your vein once every
week for 3 weeks, followed by 1 dose of cetuximab on week 4. The first dose of cetuximab was
given over 2 hours, and the weekly maintenance dose was given over 1 hour. Carboplatin was
given over 30 minutes. Every 4 weeks was considered 1 study "cycle."
There was an equal chance (50-50) for everyone in the study to be assigned to Group A or
Group B. Neither you nor your doctor could choose what group you were in, but you were told
which study treatment you would receive. You may have been assigned to Group A (Cetuximab
alone), and if the tumor got worse, you were moved to Group B (cetuximab plus carboplatin).
Now everyone on Group A who has received this new information, can move to Group B with
cetuximab plus carboplatin. The Group A portion with cetuximab alone has closed. If you
have always been on the Group A portion with cetuximab alone and want to stay there, you may
do so after talking with your doctor.
Every week, blood (about 2 teaspoons) will be drawn for routine tests.
Blood (about 3 tablespoons) will be drawn to measure circulating tumor cells after the first
1-2 weeks of treatment and then every 4 weeks.
Every 8 weeks your tumor will be measured by x-rays, CT scans, MRI, and/or other imaging
tests to check the status of your disease.
You may remain on study for as long as you are benefitting. You will be taken off study
treatment if the disease gets worse while you are on the cetuximab and carboplatin (Group
B). You will also be taken off treatment if your treatment is stopped for more than 4 weeks,
or if your doctor thinks it is best for your health. If you would like to stop on your own,
you will continue to be checked by the study staff to learn about your disease outcome.
If you go off-study, you will have an end-of-study visit. At this visit, blood (about 3
tablespoons) will be drawn to measure circulating tumor cells. You will have x-rays, CT
scans, an MRI, and/or other imaging tests to check the status of your disease.
After the end-of-study visit, you will be followed up by a phone call about every 4 months
to see how you are doing, and for your survival status.
This is an investigational study. Cetuximab is FDA approved and commercially available for
the treatment of colon cancer. Its use in this study is considered investigational.
Carboplatin is FDA approved and commercially available for the treatment of metastatic
breast cancer. Up to 100 patients will take part in this multicenter study. Up to 10
patients will be enrolled at M. D. Anderson.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Response Rate
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Francisco J. Esteva, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|UT MD Anderson Cancer Center||Houston, Texas 77030|