Cetuximab With or Without Carboplatin in Treating Women With Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00232505
First received: October 3, 2005
Last updated: July 26, 2014
Last verified: July 2014
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (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: every 8 weeks ] [ Designated as safety issue: No ]
    Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radigographic response using 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).


Secondary Outcome Measures:
  • Overall survival [ Time Frame: every 4 months ] [ Designated as safety issue: No ]
    Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.

  • Time to progression [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment


Enrollment: 112
Study Start Date: November 2005
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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
Experimental: Arm II
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
Drug: carboplatin
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare the overall response rate in women with estrogen receptor-negative, progesterone receptor-negative, 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 EGFR inhibitor on MAPK, AKT, 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 IHC and gene expression analysis.

After completion of study treatment, patients are followed every 4 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
  • CNS metastases allowed if disease is stable (no evidence of progression) ≥ 3 months after local therapy
  • No lesions identifiable only by PET scan
  • HER2 nonoverexpressing disease by IHC (0 or 1) or non-gene amplified by FISH

    • HER2 2+ by IHC allowed
  • Hormone receptor status:

    • Estrogen receptor-negative and progesterone receptor-negative tumor

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy ≥ 6 months
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine clearance ≥ 50 mL/min
  • ALT and AST ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in case of liver metastases)
  • Bilirubin ≤ 1.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant history of uncontrolled cardiac disease including, but not limited to, any of the following:

    • Uncontrolled hypertension
    • Unstable angina
    • Recent myocardial infarction (within the past 6 months)
    • Uncontrolled congestive heart failure
    • Cardiomyopathy that is either symptomatic or asymptomatic but with decreased ejection fraction < 45%
  • No history of severe infusion reaction to monoclonal antibody treatment
  • No uncontrolled infection
  • No major medical condition (i.e., uncontrolled pulmonary, renal, or hepatic dysfunction) that may affect study participation
  • No other significant comorbid condition that may compromise effective and safe participation in the study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy
  • At least 2 weeks since prior radiation therapy
  • No more than 3 prior chemotherapy regimens either in the adjuvant or metastatic setting

    • Sequential regimens (e.g., anthracycline-paclitaxel) are considered 1 regimen
  • No prior therapy that specifically and directly targets the EGFR pathway with therapeutic intent
  • No prior platinum agent for metastatic disease
  • Prior platinum agents in the adjuvant setting allowed provided there was a disease-free interval that lasted for ≥ 12 months prior to relapse
  • Concurrent bisphosphonates allowed

    • Bone lesions may not be used to measure progression or response
  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, District of Columbia, United States, 20007
Washington Cancer Institute at Washington Hospital Center
Washington, 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
St. 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
Investigators
Principal Investigator: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00232505     History of Changes
Obsolete Identifiers: NCT00420329, NCT00492375
Other Study ID Numbers: LCCC 0403, P30CA016086, CDR0000549855
Study First Received: October 3, 2005
Last Updated: July 26, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Carboplatin
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014