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

NCT ID: NCT00232505

Last Updated: 2017-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2012-08-12

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

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.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

carboplatin

Intervention Type: DRUG

Given IV

Interventions

cetuximab

Given IV

Intervention Type: BIOLOGICAL

carboplatin

Given IV

Intervention Type: DRUG

Other Intervention Names

Erbitux; Paraplatin

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Avon Foundation

OTHER

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa A. Carey, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

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

Washington Cancer Institute at Washington Hospital Center

Washington D.C., District of Columbia, 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

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

Boston, Massachusetts, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

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

Chapel Hill, North Carolina, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Rex Cancer Center at Rex Hospital

Raleigh, North Carolina, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Baylor University Medical Center - Houston

Houston, Texas, United States

Countries

United States

References

Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012 Jul 20;30(21):2615-23. doi: 10.1200/JCO.2010.34.5579. Epub 2012 Jun 4.

Reference Type: RESULT

PMID: 22665533 (View on PubMed)

Oliveras-Ferraros C, Vazquez-Martin A, Lopez-Bonet E, Martin-Castillo B, Del Barco S, Brunet J, Menendez JA. Growth and molecular interactions of the anti-EGFR antibody cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: new prospects in the treatment of triple-negative/basal-like breast cancer. Int J Oncol. 2008 Dec;33(6):1165-76.

Reference Type: DERIVED

PMID: 19020749 (View on PubMed)

Related Links

http://unclineberger.org

University of North Carolina Lineberger Comprehensive Cancer Center

Other Identifiers

M01RR000046

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CA058223

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LCCC 0403

Identifier Type: -

Identifier Source: org_study_id

NCT00420329

Identifier Type: -

Identifier Source: nct_alias

NCT00492375

Identifier Type: -

Identifier Source: nct_alias