If residual breast cancer is found in the breast or lymph node tissue removed after preoperative chemotherapy, one may be at increased risk of breast cancer recurrence in the future. The purpose of this research study is to determine if having additional treatment after preoperative chemotherapy and surgery with bevacizumab and metronomic chemotherapy would make a difference in reducing the participants chance of breast cancer recurrence compared to the standard of care, which is observation alone. This study will also evaluate the potential additional benefits from participating in an exercise and dietary intervention compared to the dietary intervention alone. Because no one knows which which post-neoadjuvant strategy is best, participants will be "randomized" to one of the study groups: 1. Diet Intervention arm, 2. Diet and Exercise Intervention Arm, 3. Bevacizumab, cyclophosphamide, methotrexate and diet intervention, 4. Bevacizumab, cyclophosphamide, methotrexate, diet and exercise intervention arm.
Bevacizumab is an antibody that is made in the laboratory. Bevacizumab works differently from the way chemotherapy drugs work. Bevacizumab works to slow or stop the growth of cells in cancer tumors by decreasing the blood supply to tumors. Bevacizumab has been approved by the U.S Food and Drug Administration to treat advanced colorectal, lung and kidney cancers. Metronomic chemotherapy also attacks tumor blood supply. Standard chemotherapy drugs are used, cyclophosphamide and methotrexate (CM), but in very small daily doses by mouth, well below the threshold where they can cause people to feel sick. Previous research studies have shown that women with breast cancer who take metronomic CM and bevacizumab feel very well, and the combination therapy is active in reducing their cancer. Participants in this study will also be provided with diet or diet and exercise counseling over the telephone. Studies have shown that many women who are treated for breast cancer will gain weight during and after their treatment, and may also experience fatigue and weakness. Many studies have shown that making changes in diet and increasing exercise can help prevent weight gain and also may increase energy and decrease other side effects of chemotherapy and other breast cancer treatments.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
55
University of Alabama at Birmingham
Birmingham, Alabama, United States
Indiana Unversity Simon Cancer Center
Indianapolis, Indiana, United States
Faulkner Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
Milford, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Median 3-year Recurrence-free Survival (RFS)
RFS events is defined as the duration of time from randomization to time of an RFS event, marked as positive if any of listed event shows: local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive), any other second cancer (excluding non-melanomatous skin cancer or cervical cancer in situ), or death from any cause. The diagnosis of local or distant recurrence should be pathologically confirmed however if biopsy if not possible, radiology confirmation acceptable.
Time frame: Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Feasibility Rate
The feasibility of post-adjuvant maintenance metronomic chemotherapy is open to women with hormone receptor negative tumors and either node negative or node positive disease.
Time frame: 2 years
Number of Serious Adverse Event of Bevacizumab
Adverse event evaluations will occur at each study visit throughout the treatment period of 2 years and will continue every 6 months during the follow-up period. Only Grade 3/4 AE (CTCAE v4) was reported.
Time frame: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.
Number of Serious Adverse Event of Metronomic Chemotherapy
Adverse event evaluations will occur at each study visit throughout the treatment period of 2 years and will continue every 6 months during the follow-up period. Only Grade 3/4 AE (CTCAE v4) was reported.
Time frame: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.
Number of Serious Adverse Event (AE) of Lifestyle
Exercise and/or dietary lifestyle interventions defined per protocol. The lifestyle intervention will be administered by telephone, supplemented with a participant workbook (Appendix 9 in protocol). Only Grade 3/4 AE (CTCAE v4) was reported.
Time frame: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.
Change in Level of Fasting Insulin
Change in level of fasting insulin from baseline at study entry to 6 months.
Time frame: Baseline and 6 months
Change in Body Weight
data not collected due to early termination of the study.
Time frame: Baseline and 6 months
Change in IGF-1
Change in level of insulin-like growth factor -1 (IGF-1) from baseline at study entry to 6 months.
Time frame: Baseline and 6 months
Changes in Diet and Physical Activity Upon Biomarkers
To evaluate the impact of changes in diet and physical activity upon biomarkers associated with breast cancer risk and prognosis, including leptin, adiponectin, testosterone, estradiol and inflammatory mediators (including: TNF alpha, IL-1 beta, IL-2, IL-5, IL-6, IL-8, IL-10, and IL-12)
Time frame: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon biomarkers
Changes in Physical Activity and Dietary Behaviors
Time frame: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon physical activity
Impact Upon Anthropometric Measures, Quality of Life and Fatigue
Time frame: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon physical activity
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