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Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2-Nonoverexpressing Metastatic Breast Cancers


Phase 2
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

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
closed.

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.


Inclusion Criteria:



1. At least 18 years of age

2. Metastatic breast cancer (Stage IV) with measurable disease by RECIST criteria

3. No more than three prior chemotherapy regimens either in the adjuvant or metastatic
setting.

4. Histologically documented (either primary or metastatic site) breast cancer that is
ER-negative. PR-negative, and HER-2 nonoverexpressing by immunohistochemistry (0,1)
or non-gene amplified by FISH performed upon the primary tumor or metastatic lesion.
HER-2 2+ by immunohistochemistry is usually negative by FISH, and this confirmatory
test should be performed when possible, however may participate if fulfill other
criteria.

5. Completion of prior chemotherapy at least 3 weeks prior to study entry.

6. Patients may have received therapy (ies) in the adjuvant or metastatic setting,
however must have discontinued prior to entry. Patients may receive concurrent
bisphosphonates, however if taking bisphosphonates, bone lesions may not be used for
progression or response.

7. Radiation therapy must be completed at least 2 weeks prior to study entry, and
radiated lesions may not serve as measurable disease.

8. Patients may have CNS metastases if stable (no evidence of progression) for at least
3 months after local therapy.

9. ECOG performance status 0-2 and life expectancy of at least 6 months.

10. Adequate organ function defined as: ANC greater than or equal to 1,500/mm3, platelets
greater than or equal to 100,000/mm3, creatinine clearance greater than 50mL/min, ALT
and AST lower than 2.5 x upper limit of normal (ULN) (or lower than 5 x ULN in case
of liver metastases); total bilirubin lower than 1.5 mg/dL.

11. Tissue block available for EGFR studies is recommended, although will not exclude
patients from participating.

12. Pregnant or lactating women will be excluded. Women of child bearing potential must
have documented negative pregnancy test within two weeks of study entry and agree to
acceptable birth control during the duration of the study therapy.

13. Signed written informed consent.

Exclusion Criteria:

1. Lesions identifiable only by PET.

2. More than three prior chemotherapy regimens (including adjuvant). Sequential regimens
such as AC-paclitaxel are considered one regimen.

3. Prior therapy which specifically and directly targets the EGFR pathway with
therapeutic intent.

4. Prior platinum agent for metastatic disease. If platinum agent was used adjuvantly,
the patient must have had at least 12 months disease-free interval prior to relapse.

5. Prior severe infusion reaction to a monoclonal antibody.

6. Major medical conditions that might affect study participation (uncontrolled
pulmonary, renal, or hepatic dysfunction, uncontrolled infection).

7. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
congestive heart failure, and cardiomyopathy that is either symptomatic or
asymptomatic but with decreased ejection fraction lower than 45%.

8. Other significant comorbid condition which the investigator feels might compromise
effective and safe participation in the study.

9. Inability to comply with the requirements of the study.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall Response Rate

Outcome Description:

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.

Outcome Time Frame:

9 Years

Safety Issue:

Yes

Principal Investigator

Francisco J. Esteva, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2006-0183

NCT ID:

NCT00420329

Start Date:

December 2006

Completion Date:

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • ER-Negative
  • PR-Negative
  • HER-2-Nonoverexpressing
  • Carboplatin
  • Paraplatin®
  • Cetuximab
  • C225
  • Erbitux™
  • IMC-C225
  • Breast Neoplasms

Name

Location

UT MD Anderson Cancer CenterHouston, Texas  77030