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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

October 3, 2005
July 26, 2014
November 2005
December 2014   (final data collection date for primary outcome measure)
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).
- Overall response rate to single agent cetuximab and to combination cetuximab plus carboplatin
Complete list of historical versions of study NCT00232505 on ClinicalTrials.gov Archive Site
  • 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
  • - Time to disease progression
  • - To correlate downstream effects of EGFR inhibitor on MAPK, AKT, Ki67 and EGFR-dependent signaling, proliferation, and apoptosis and correlate these with toxicity and response in patients with accessible tumors.
  • - To examine changes in above markers and gene expression in circulating tumor cells during therapy
  • - Overall survival
Not Provided
Not Provided
 
Cetuximab With or Without Carboplatin in Treating Women With 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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Breast Cancer
  • Biological: cetuximab
    Given IV
  • Drug: carboplatin
    Given IV
  • 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.
    Intervention: Biological: cetuximab
  • 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.
    Interventions:
    • Biological: cetuximab
    • Drug: carboplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
112
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00232505
LCCC 0403, P30CA016086, CDR0000549855
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Lisa A. Carey, MD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP