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Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Biological: cetuximab
Drug: carboplatin
Registration Number
NCT00232505
Lead Sponsor
UNC Lineberger Comprehensive Cancer Center
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
112
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CetuximabcetuximabPatients 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.
Cetuximab and CarboplatincetuximabPatients 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.
Cetuximab and CarboplatincarboplatinPatients 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.
Primary Outcome Measures
NameTimeMethod
Overall Disease Response Rate5 years

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

Secondary Outcome Measures
NameTimeMethod
Overall SurvivalEvery four months until death of any cause or end of data collection up to 40 months

Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.

Progression-Free SurvivalEvery four months until progression, death of any cause, or end of data collection up to 40 months

Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment

Trial Locations

Locations (14)

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Washington University School of Medicine

🇺🇸

Saint Louis, Missouri, United States

Baylor University Medical Center - Houston

🇺🇸

Houston, Texas, United States

Indiana University Melvin and Bren Simon Cancer Center

🇺🇸

Indianapolis, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

🇺🇸

Baltimore, Maryland, United States

Washington Cancer Institute at Washington Hospital Center

🇺🇸

Washington, D.C., District of Columbia, United States

Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

🇺🇸

Birmingham, Alabama, United States

UCSF Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

🇺🇸

Washington, D.C., District of Columbia, United States

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Duke Comprehensive Cancer Center

🇺🇸

Durham, North Carolina, United States

M. D. Anderson Cancer Center at University of Texas

🇺🇸

Houston, Texas, United States

Rex Cancer Center at Rex Hospital

🇺🇸

Raleigh, North Carolina, United States

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