Study Stopped
The study was terminated early due to slow accrual.
Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer
ABCDE
ABCDE: A Phase II Randomized Study of Adjuvant Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer
2 other identifiers
interventional
55
1 country
9
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 breast-cancer
Started Sep 2010
Longer than P75 for phase_2 breast-cancer
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 19, 2009
CompletedFirst Posted
Study publicly available on registry
June 22, 2009
CompletedStudy Start
First participant enrolled
September 1, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 30, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2019
CompletedResults Posted
Study results publicly available
January 19, 2022
CompletedJanuary 19, 2022
December 1, 2021
4.4 years
June 19, 2009
September 20, 2021
December 20, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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.
Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.
Secondary Outcomes (10)
Feasibility Rate
2 years
Number of Serious Adverse Event of Bevacizumab
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
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
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
Baseline and 6 months
- +5 more secondary outcomes
Study Arms (4)
Lifestyle: Diet
EXPERIMENTALThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.
Lifestyle: Diet+Exericise
EXPERIMENTALThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.
Lifestyle: Diet and Bevicizumab+CM
EXPERIMENTALThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Lifestyle: Diet+Exericise and Bevicizumab+CM
EXPERIMENTALThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Interventions
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed invasive breast cancer. HER2 positive disease is not allowed. Metastatic breast cancer (Stage IV) is not allowed.
- For patients entering the trial after neoadjuvant chemotherapy, there must be the presence of residual invasive disease on pathologic review following neoadjuvant chemotherapy. Residual disease is defined as a Miller-Payne response in the breast of 0-4 and/or residual carcinoma in one or more regional lymph nodes that would meet AJCC 7th edition criteria for N1 - N3 disease. The presence of DCIS without invasion does not qualify as residual disease. Alternatively, if Miller-Payne grading is not available, the patient will be eligible if the pathology report indicates any residual invasive carcinoma following neoadjuvant therapy.
- If tumor is triple negative (ER-/PR-/HER2-) and the patient received neoadjuvant chemotherapy, disease may be clinical stage I-III pre-operatively, per AJCC 7th edition, based on baseline evaluation by clinical examination and/or breast imaging. Patients must have the presence of residual invasive disease on pathologic review following their neoadjuvant chemotherapy.
- If tumor is triple negative and the patient did not receive neoadjuvant chemotherapy, there must be pathologic lymph node positivity and Stage IIB or greater disease after surgery. For the purposes of eligibility, lymph node positivity can refer to either axillary or intramammary lymph nodes.
- If tumor is hormone receptor positive, disease must be clinical Stage III neoadjuvantly, per AJCC 7th edition, based on baseline evaluation by clinical examination and/or breast imaging, or pathologic Stage IIB or greater at time of definitive surgery. Patients with hormone receptor positive breast cancer who do not receive neoadjuvant chemotherapy are not eligible for this protocol.
- For patients who completed neoadjuvant chemotherapy, the regimen must contain an anthracycline, a taxane, or both. Patients who have received neoadjuvant therapy as part of a clinical trial are acceptable. Protocol therapy must be initiated \< 180 days after last surgery for breast cancer. For triple negative patients who receive adjuvant chemotherapy only, the regimen must contain both an anthracycline and a taxane. For these patients, protocol therapy must be initiated \< 28 weeks after initiation of adjuvant chemotherapy.
- Patients with ER+ and/or PR+ breast cancer should receive adjuvant hormonal therapy
- No prior exposure to bevacizumab or other inhibitors of angiogenesis is allowed.
- Patients must have completed definitive resection of primary tumor. Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however positive margins are acceptable if the treatment team believes no further surgery is possible and patient has received radiotherapy. Patients with margins positive for lobular carcinoma in situ are eligible.
- Post-mastectomy radiotherapy is suggested for all patients with a primary tumor 5cm or greater or involvement of 4 or more lymph nodes. Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy, partial mastectomy, and excisional biopsy.
- Patients must have the presence of residual invasive disease on pathologic review following their preoperative chemotherapy. The presence of DCIS without invasion does not qualify as residual disease. Alternatively, if Miller-Payne grading is not available, the patient will be eligible if the pathology report indicates any residual invasive carcinoma following preoperative therapy.
- LVEF equal to or greater than institutional limits of normal after preoperative chemotherapy, as assessed by echocardiogram, within 30 days prior to registration
- ECOG Performance Status 0-1 within 2 weeks of registration
- years of age or greater
You may not qualify if:
- Laboratory assessments as outlined in the protocol
- Stage IV breast cancer. Patients with metastatic disease are ineligible. However, specific staging studies are not required in the absence of symptoms
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History if myocardial infarction or unstable angina within 12 months prior to registration
- History of stroke or transient ischemic attack at any time
- Significant vascular disease within 6 months prior to registration
- History of hemoptysis within 1 month prior to registration
- Ongoing or active infection
- NYHA Grade II or greater congestive heart failure
- Unstable angina pectoralis
- Psychiatric illness/social situations that would limit compliance with study requirements
- Evidence of bleeding diathesis or significant coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to registration
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to registration
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Brigham and Women's Hospitalcollaborator
- Beth Israel Deaconess Medical Centercollaborator
- Translational Breast Cancer Research Consortiumcollaborator
- Genentech, Inc.collaborator
Study Sites (9)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Indiana Unversity Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Faulkner Hospital
Boston, Massachusetts, 02130, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
Milford, Massachusetts, 01757, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Related Publications (1)
Trapani D, Jin Q, Miller KD, Rugo HS, Reeder-Hayes KE, Traina T, Abdou Y, Falkson C, Abramson V, Ligibel J, Chen W, Come S, Nohria A, Ryabin N, Tayob N, Tolaney SM, Burstein HJ, Mayer EL. Optimizing Postneoadjuvant Treatment of Residual Breast Cancer With Adjuvant Bevacizumab Alone, With Metronomic or Standard-Dose Chemotherapy: A Combined Analysis of DFCI 05-055 and DFCI 09-134/TBCRC 012/ABCDE Clinical Trials. Clin Breast Cancer. 2025 Jun;25(4):e419-e430.e5. doi: 10.1016/j.clbc.2024.12.018. Epub 2024 Dec 31.
PMID: 39890560DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated early due to slow accrual and therefore interpretation of results is limited.
Results Point of Contact
- Title
- Erica Mayer MD MPH
- Organization
- Dana-Farber Cancer Institute
Study Officials
- STUDY CHAIR
Erica Mayer, MD
Dana-Farber Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Erica Mayer, M.D.
Study Record Dates
First Submitted
June 19, 2009
First Posted
June 22, 2009
Study Start
September 1, 2010
Primary Completion
January 30, 2015
Study Completion
January 30, 2019
Last Updated
January 19, 2022
Results First Posted
January 19, 2022
Record last verified: 2021-12
Data Sharing
- IPD Sharing
- Will not share