This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Bristol-Myers Squibb
Avon Foundation
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00232505
First received: October 3, 2005
Last updated: May 25, 2017
Last verified: May 2017
  Purpose

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.


Condition Intervention Phase
Breast Cancer Biological: cetuximab Drug: carboplatin Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Overall Disease Response Rate [ Time Frame: 5 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:
  • Overall Survival [ Time Frame: Every 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 Survival [ Time Frame: Every 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


Enrollment: 112
Actual Study Start Date: November 2005
Study Completion Date: August 12, 2012
Primary Completion Date: June 21, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: cetuximab
Given IV
Other Name: Erbitux
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.
Biological: cetuximab
Given IV
Other Name: Erbitux
Drug: carboplatin
Given IV
Other Name: Paraplatin

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.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00232505

Locations
United States, Alabama
Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, D.C., District of Columbia, United States, 20007
Washington Cancer Institute at Washington Hospital Center
Washington, D.C., District of Columbia, United States, 20010
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, United States, 27607
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Bristol-Myers Squibb
Avon Foundation
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00232505     History of Changes
Obsolete Identifiers: NCT00420329, NCT00492375
Other Study ID Numbers: LCCC 0403
M01RR000046 ( U.S. NIH Grant/Contract )
CA058223 ( Other Grant/Funding Number: NCI OSP/SPOREs )
Study First Received: October 3, 2005
Results First Received: April 7, 2017
Last Updated: May 25, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
recurrent breast cancer
stage IV breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carboplatin
Cetuximab
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 22, 2017