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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00232505
• Other study ID #: LCCC 0403
• Secondary ID: M01RR000046CA058
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2005
• Last updated: March 15, 2017
• Start date: November 2005
• Est. completion date: August 12, 2012

Study information

• Verified date: March 2017
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00420329
• NCT00492375

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: August 12, 2012
• Est. primary completion date: June 21, 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• cetuximab
Given IV

Drug:
• carboplatin
Given IV

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
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	Baylor University Medical Center - Houston	Houston	Texas
United States	M. D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Rex Cancer Center at Rex Hospital	Raleigh	North Carolina
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Washington University School of Medicine	St. Louis	Missouri
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia

Sponsors (5)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	Avon Foundation, Bristol-Myers Squibb, National Cancer Institute (NCI), National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall disease response rate	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).	every 8 weeks
Secondary	Overall survival	Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival.	every 4 months
Secondary	Time to progression	Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment	every 8 weeks