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Title
TBCRC 001: Comparison and effectiveness of cetuximab alone or cetuximab with carboplatin in women
with triple negative, metastatic breast cancer (MBC)
Purpose of the Study
Breast cancers can be categorized by subtypes. This study looked at the subtype referred to as triple
negative breast cancer. Triple negative breast cancer lacks three common characteristics: the estrogen
receptor (ER) protein, the progesterone receptor (PR) protein, and the human epidermal growth factor
receptor 2 (HER2). Currently available treatments can target each of these markers. Unfortunately, no
such “targeted” therapy has yet been found that is effective in triple negative breast cancer. Many triple
negative breast cancers have been shown to have high expression of another protein, the epidermal
growth factor receptor protein (EGFR). Thus, it is hoped that drugs that target that protein may be
effective. Cetuximab is a drug that has been approved for EGFR expressing colon cancer and may be of
use in triple negative breast cancer.
TBCRC 001 enrolled 102 women with triple negative, metastatic, (stage 4) breast cancer who were put
into groups by chance and assigned to receive cetuximab alone or cetuximab with carboplatin.
Cetuximab was being evaluated to see if it could block the epidermal growth factor pathway and stop the
cancer from growing either alone or in combination with the chemotherapy, carboplatin. In addition, the
trial collected tumor and blood samples to evaluate the biologic as well as the clinical response.
Sponsor(s)
National Cancer Institute; Bristol Myers Squibb
Participating Sites
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Baylor College of Medicine
Duke University Medical Cancer Center
Dana-Farber/ Harvard Cancer Center
Georgetown University
Indiana University Simon Cancer Center
Johns Hopkins University
Mayo Clinic Cancer Center
MD Anderson Cancer Center
University of Alabama, Birmingham
University of California, San Francisco
University of North Carolina, Chapel Hill
Washington University
Start Date & Stop Date
Date First Site Activated: October, 2005
Date Trial Closed to Enrollment: October, 2007
Key Eligibility Requirements
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Metastatic (stage 4) breast cancer with measurable disease
Triple negative (ER negative, PR negative, and HER2 negative)
No more than 3 prior chemotherapy regimens
No prior EGFR inhibitor or platinum for metastatic disease
No significant organ dysfunction
Central nervous system (CNS) only if involvement is stable for at least 3 months
At least 6 months’ life expectancy
Study Design
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Eligible women were assigned by chance (randomized) as follows:
o Group 1 - cetuximab alone with carboplatin added when the cancer started to grow
o Group 2 - combination cetuximab plus carboplatin from the beginning
Participating women had their tumors measured every 8 weeks using either CT or MRI scans.
Treatment was stopped if the disease was growing, if the side effects were not tolerable, or if
patients chose to stop.
Willing women were asked to permit biopsies of the tumor before starting therapy, and again 7
days after beginning treatment in order to examine drug impact on the tumor.
Results
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102 women enrolled in this trial, and most of their tumors were the triple negative subtype
Fewer than 10% responded to the cetuximab alone, which was expected.
18% responded to the combination of cetuximab plus carboplatin
31% of those who responded had their cancer controlled for at least 6 months. This was better
than expected from standard therapy, although not as good as we had hoped.
Most patients experienced rapid disease progression with only a 2-month average time before the
disease started growing again.
Neither treatment caused serious side effects. Ten percent of women had rash, fatigue and
nausea and vomiting that was generally mild.
Biopsy and blood samples offered insight into this cancer subtype.
18 women allowed repeated biopsies of their tumors before and after therapy.
Interestingly, the women that responded to the anti-EGFR drug showed an EGFR pathway that
was turned “on” initially and then turned “off” by the drug. This is exciting because it proves that
the drug was doing what it was supposed to in those tumors, and discouraging because so many
of the tumors had other ways to grow that this therapy didn’t affect.
Next Steps
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Women who participated in this study have helped to advance our understanding of the disease,
moving us forward in the search for markers of cancer activity and better treatment options.
It is not likely there will be one best treatment for patients with triple negative breast cancer.
Future trials will be developed to examine other characteristics that appear important for triple
negative breast cancer.
Scientific Publications Available for this Clinical Trial
Carey, L.A., Mayer, E., Marcom, P.K., Rugo, H., Liu, M., Ma, C., Rimawi, M., Storniolo, A., Forero, A.,
Esteva, F., Wolff, A., Ingle, J., Ferraro, M., Sawyer, L., Davidson, N., Perou, C.M., Winer, E.P. TBCRC
001: EGFR Inhibition with Cetuximab in Metastatic Triple Negative (Basal-Like) Breast Cancer. 2007
SABCS, Poster #307.
Carey, L.A., Rugo, H.S., Marcom, P.K., Irvin, W., Ferraro, M., Burrows, E., He, X., Perou, C.M., Winer,
E.P. (TBCRC). TBCRC 001: EGFR Inhibition with Cetuximab Added to Carboplatin in Metastatic TripleNegative (Basal-like) Breast Cancer. 2008 ASCO, Oral Presentation, Abstract #1009.
Rugo, H.S., Carey, L.A., Mayer, E., Burrows, E., Scott, J., Moore, D., Park, J.W. (TBCRC). Assays of
Circulating Tumor Cells and Outcome in the Triple Negative Breast Cancer Trial TBCRC 001. 2008
Molecular Markers, Poster, Abstract #2.
Carey, L., O’Shaughnessy, J.A., Hoadley, K., Khambata-Ford, S., Horak, C.E., Xu, L., Awad, M.,
Brickman, D., Muller, S., Donato, J., Asmar, L., Stiljeman, I., Ebbert, M., Bernard, P., Perou, C.M.
Potential predictive markers of benefit from cetuximab in metastatic breast cancer: an analysis of two
randomized Phase 2 trials. 2009 SABCS, Poster.
Carey, L.A., Rugo, H.S., Marcom, P.K., Mayer, E.L., Esteva, F.J., Ma, C.X., Liu, M.C., Storniolo, A.M.,
Rimawi, M.F., Forero-Torres, A., Wolff, A.C., Hobday, T.J., Ivanova, A., Chiu, W., Ferraro, M., Burrows,
E., Bernard, P.S., Hoadley, K.A., Perou, C.M., Winer, E.P. TBCRC 001: Randomized Phase II Study of
Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer. J Clin Oncol 30
(21): 2012.
Tao, J., Castel, P., Radosevic-Robin, N., Elkabets, M., Auricchio, N., Aceto, N., Weitsman, G., Barber, P.,
Vojnovic, B., Ellis, H., Morse, N., Viola-Villegas, N.T., Campos, A.B., Juric, D., Hazra, S., Singh, S., Kim,
P., Bergamaschi, S., Maheswaran, S., Ng, T., Penault-Llorca, F., Lewis, J.S., Carey, L.A., Perou, C.M.,
Baselga, J., Scaltriti, M. Antagonism of EGFR and HER3 enhances the response to inhibitors of the
PI3K/Akt pathway in triple negative breast cancer. Science Signaling 7 (318): 2014.
Magbanua, M.J.M., Carey, L.A., DeLuca, A., Hwang, J., Scott, J.H., Rimawi, M.F., Mayer, E.L., Marcom,
P.K., Liu, M.C., Esteva, F.J., Park, J.W., Rugo, H.S. Circulating tumor cell analysis in metastatic triplenegative breast cancers. Clinical Cancer Research 21 (5): 2015.
Link to the NCI Summary on ClinicalTrials.gov
NCT00232505
*This summary was reviewed by: Lisa Carey, M.D. This summary was also reviewed and approved by the members of the TBCRC
Patient Advocate Working Group.