Tamoxifen Citrate or Letrozole With or Without Bevacizumab in Treating Women With Stage III or Stage IV Breast Cancer
Summary
This randomized phase III trial is studying giving tamoxifen citrate or letrozole together with bevacizumab to see how well it works compared with tamoxifen citrate or letrozole alone in treating women with stage III or stage IV breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen* or letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving hormone therapy is more effective with or without bevacizumab in treating advanced breast cancer
Description
PRIMARY OBJECTIVES:
I. To compare the progression-free survival of women with estrogen- and/or progesterone-receptor-positive stage IIIB-IV breast cancer treated with letrozole with vs without bevacizumab as first-line treatment.
SECONDARY OBJECTIVES:
I. To compare the proportion of patients receiving letrozole with or without bevacizumab who remain progression-free at 6 and 12 months.
II. To compare the incidence of objective response (complete response [CR] + partial response [PR]) in patients receiving letrozole with or without bevacizumab, as determined by RECIST criteria, excluding patients with non-measurable disease.
III. To compare the incidence of clinical benefit (CR + PR + stable disease >= 6 months) in patients receiving letrozole with or without bevacizumab.
IV. To compare the duration of objective response in patients receiving letrozole with or without bevacizumab.
V. To compare the time to treatment failure, defined as the interval from randomization until progression, toxicity, withdrawn consent, or going onto non protocol therapy, in patients receiving letrozole with or without bevacizumab.
VI. To compare the overall survival of patients receiving letrozole with or without bevacizumab, including the probability of survival until 36 months.
V. To compare toxicity levels of bevacizumab in both the letrozole-treated patients and in the tamoxifen-treated* patients.
VI. To compare progression-free survival and overall survival of all patients receiving endocrine therapy with and without bevacizumab (by combining both letrozole and tamoxifen* patient subgroups). NOTE: *As of 5/15/2011, patients only receive letrozole.
OUTLINE: This is a multicenter study. Patients are stratified according to planned endocrine therapy* (letrozole vs tamoxifen*), disease measurability (no vs yes), and disease-free interval from initial diagnosis to first progression (≤ 24 months vs > 24 months). Patients are randomized to 1 of 2 treatment arms.
NOTE: The placebo-controlled portion of the study was canceled on 5-15-10
ARM I: Patients receive oral endocrine therapy* (tamoxifen citrate or letrozole) once daily on days 1-21 and bevacizumab IV on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oral endocrine therapy* (tamoxifen citrate or letrozole) once daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 6 months for the first 2 years and then annually for up to 3 years.
NOTE: As of 5/15/2011, patients only receive letrozole.
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Recurrent Breast Cancer
Intervention
tamoxifen citrate, letrozole, bevacizumab
Location
Providence Hospital
Mobile
Alabama
United States
36608
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00601900
- Information obtained from ClinicalTrials.gov on April 16, 2013
Medical and Biotech [MESH] Definitions
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
Carcinoma, Lobular
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Mucin-1
Carbohydrate antigen elevated in patients with tumors of the breast, ovary, lung, and prostate as well as other disorders. The mucin is expressed normally by most glandular epithelia but shows particularly increased expression in the breast at lactation and in malignancy. It is thus an established serum marker for breast cancer.
Breast Neoplasms
Tumors or cancer of the human BREAST.
Brca1 Protein
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
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