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Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer


Phase 2
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

Thank you

Trial Information

Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Overall disease response rate

Outcome Description:

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).

Outcome Time Frame:

every 8 weeks

Safety Issue:

No

Principal Investigator

Lisa A. Carey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC 0403

NCT ID:

NCT00232505

Start Date:

November 2005

Completion Date:

December 2014

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IV breast cancer
  • Breast Neoplasms

Name

Location

Mayo Clinic Cancer CenterRochester, Minnesota  55905
Washington University School of MedicineSaint Louis, Missouri  63110
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Washington Cancer Institute at Washington Hospital CenterWashington, District of Columbia  20010
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Lombardi Comprehensive Cancer Center at Georgetown University Medical CenterWashington, District of Columbia  20007
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Lurleen Wallace Comprehensive Cancer at University of Alabama - BirminghamBirmingham, Alabama  35294
Rex Cancer Center at Rex HospitalRaleigh, North Carolina  27607