First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU

Stage IV Breast Cancer Clinical Trial

Official title: A Randomized Phase III Double-Blind Placebo-Controlled Trial of First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab for Patients With HER-2/NEU Over-Expressing Metastatic Breast Cancer

Status Active, not recruiting

Clinical Trial Summary

This randomized phase III trial studies first-line chemotherapy and trastuzumab to compare how well they work when given with or without bevacizumab in treating patients with breast cancer that overexpresses human epidermal growth factor receptor 2 (HER-2/NEU) and has spread to other areas of the body. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as trastuzumab and bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking the growth of new blood vessels necessary for tumor growth. It is not yet known whether giving first-line chemotherapy together with trastuzumab is more effective with or without bevacizumab in treating patients with metastatic breast cancer that overexpresses HER-2/NEU.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Evaluate efficacy of the addition of bevacizumab in patients eligible for first-line trastuzumab with chemotherapy for HER-2/NEU overexpressing metastatic breast cancer, by assessing the progression-free survival (PFS) after initiation of combination therapy.

SECONDARY OBJECTIVES:

I. Evaluate response rates (RR) in patients with measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST]), when applicable.

II. Evaluate overall survival (OS). III. Evaluate time to progression (TTP). IV. Evaluate the percent of patients who are progression-free (PPF) at 6 months.

V. Compare the toxicity of chemotherapy/trastuzumab to that of chemotherapy/trastuzumab in combination with bevacizumab.

VI. Compare breast cancer symptoms and treatment related symptoms between patients receiving chemotherapy and trastuzumab with or without bevacizumab.

VII. Evaluate whether PFS correlates with vascular endothelial growth factor (VEGF) levels in breast tumor tissue.

VIII. Analysis of circulating tumor cells and circulating endothelial cells (CEC).

IX. Serially enumerate circulating tumor cells (CTC) and CEC in patients on study and determine whether: the number of CTC and CEC decrease in responding patients; the extent of CTC and CEC decrease is greater in the experimental arm, Arm B versus the control arm, Arm A; enumeration of CTC and CEC in responding patients correlate with progression free survival (PFS).

X. Perform an exploratory analysis of phosphorylation status of v-akt murine thymoma viral oncogene homolog (akt)-2 in circulating tumor cells.

XI. Perform an exploratory analysis of reverse transcriptase (RT)-polymerase chain reaction (PCR) of CTC messenger ribonucleic acid (mRNA) to determine whether change in expression of selected downstream targets of bevacizumab therapy can serve as pharmacodynamic or surrogate markers of bevacizumab targeting and modulation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A:

INDUCTION THERAPY: Patients receive trastuzumab intravenously (IV) over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 10 years. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Breast Neoplasms, Male
• Carcinoma
• HER2/Neu Positive
• Male Breast Carcinoma
• Recurrent Breast Carcinoma
• Stage IV Breast Cancer

• NCT number: NCT00520975
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 2007