- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00232505
Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer
Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving cetuximab together with carboplatin is more effective than giving cetuximab alone in treating metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying cetuximab and carboplatin to see how well they work compared with cetuximab alone in treating women with estrogen receptor-negative (ER-), progesterone receptor-negative (PR-) metastatic breast cancer.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- Compare the overall response rate in women with estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor 2 (HER2)-nonoverexpressing metastatic breast cancer treated with cetuximab with vs without carboplatin.
Secondary
- Compare the time to disease progression in patients treated with these regimens.
- Correlate downstream effects of epidermal growth factor receptor (EGFR) inhibitor on Mitogen-activated protein kinases (MAPK), Protein kinase B (AKT), monoclonal antibody Ki-67 (Ki67), and EGFR-dependent signaling, proliferation, and apoptosis with toxicity and response in patients with accessible tumors treated with these regimens.
- Determine the changes in biomarkers and gene expression in circulating tumor cells during treatment.
- Compare the overall survival rate in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cetuximab IV over 60-120 minutes once a week.
- Arm II: Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients not responding to treatment in arm I may cross over to arm II.
Blood samples are collected periodically throughout study for correlative biomarker analysis by Immunohistochemistry (IHC) and gene expression analysis.
After completion of study treatment, patients are followed every 4 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Alabama
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Birmingham, Alabama, United States, 35294
- Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
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California
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San Francisco, California, United States, 94115
- UCSF Comprehensive Cancer Center
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District of Columbia
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Washington, D.C., District of Columbia, United States, 20010
- Washington Cancer Institute at Washington Hospital Center
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Washington, D.C., District of Columbia, United States, 20007
- Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
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Indiana
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Indianapolis, Indiana, United States, 46202-5289
- Indiana University Melvin and Bren Simon Cancer Center
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Maryland
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Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Cancer Center
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University School of Medicine
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North Carolina
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Chapel Hill, North Carolina, United States, 27599-7295
- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
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Durham, North Carolina, United States, 27710
- Duke Comprehensive Cancer Center
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Raleigh, North Carolina, United States, 27607
- Rex Cancer Center at Rex Hospital
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Texas
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Houston, Texas, United States, 77030-4009
- M. D. Anderson Cancer Center at University of Texas
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Houston, Texas, United States, 77030
- Baylor University Medical Center - Houston
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed breast cancer
- Metastatic (stage IV) disease
Measurable disease by RECIST criteria
- Irradiated lesions are not considered measurable disease
- Central nervous system (CNS) metastases allowed if disease is stable (no evidence of progression) ≥ 3 months after local therapy
- No lesions identifiable only by positron emission tomography (PET) scan
HER2 nonoverexpressing disease by IHC (0 or 1) or non-gene amplified by Fluorescence In Situ Hybridization (FISH)
- HER2 2+ by IHC allowed
Hormone receptor status:
- Estrogen receptor-negative and progesterone receptor-negative tumor
Inclusion Criteria
- At least 18 years of age
- Metastatic breast cancer (Stage IV) with measurable disease by RECIST criteria
- No more than three prior chemotherapy regimens either in the adjuvant or metastatic setting.
- Histologically documented (either primary or metastatic site) breast cancer that is estrogen receptor- (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.
- Completion of prior chemotherapy at least 3 weeks prior to study entry.
- 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.
- Radiation therapy must be completed at least 2 weeks prior to study entry, and radiated lesions may not serve as measurable disease.
- Patients may have CNS metastases if stable (no evidence of progression) > 3 months after local therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and life expectancy of at least 6 months.
- Adequate organ function defined as:absolute neutrophil count (ANC) > 1500/mm3, plts > 100,000/mm3, creatinine clearance >50 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) (or ≤5 x ULN in case of liver metastases); total bilirubin ≤1.5 mg/dL.
- Tissue block available for EGFR studies is recommended, although will not exclude patients from participating.
- 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.
- Signed written informed consent.
Exclusion Criteria
- Lesions identifiable only by PET.
- More than three prior chemotherapy regimens (including adjuvant). Sequential regimens such as doxorubicin and cyclophosphamide followed by paclitaxel (AC-paclitaxel) are considered one regimen.
- Prior therapy which specifically and directly targets the EGFR pathway with therapeutic intent.
- 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.
- Prior severe infusion reaction to a monoclonal antibody.
- Major medical conditions that might affect study participation (uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection).
- 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 <45%
- Other significant comorbid condition which the investigator feels might compromise effective and safe participation in the study.
- Inability to comply with the requirements of the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cetuximab
Patients receive cetuximab IV over 60-120 minutes once a week.
Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients not responding to treatment may cross over to arm II.
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Given IV
Other Names:
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Experimental: Cetuximab and Carboplatin
Patients receive cetuximab as in arm I and carboplatin IV on days 1, 8, and 15.
Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
|
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Disease Response Rate
Time Frame: 5 years
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Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radiographic response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria every 8 weeks until subject experiences disease progression.
Overall response will be measured as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD).Per RECIST v1.0 for target lesions and assessed by CT (spiral): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression
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5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: Every four months until death of any cause or end of data collection up to 40 months
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Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.
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Every four months until death of any cause or end of data collection up to 40 months
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Progression-Free Survival
Time Frame: Every four months until progression, death of any cause, or end of data collection up to 40 months
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Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment
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Every four months until progression, death of any cause, or end of data collection up to 40 months
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Lisa A. Carey, MD, UNC Lineberger Comprehensive Cancer Center
Publications and helpful links
General Publications
- Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012 Jul 20;30(21):2615-23. doi: 10.1200/JCO.2010.34.5579. Epub 2012 Jun 4.
- Oliveras-Ferraros C, Vazquez-Martin A, Lopez-Bonet E, Martin-Castillo B, Del Barco S, Brunet J, Menendez JA. Growth and molecular interactions of the anti-EGFR antibody cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: new prospects in the treatment of triple-negative/basal-like breast cancer. Int J Oncol. 2008 Dec;33(6):1165-76.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- LCCC 0403
- M01RR000046 (U.S. NIH Grant/Contract)
- CA058223 (Other Grant/Funding Number: National Cancer Institute)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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