Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer (ABCDE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Translational Breast Cancer Research Consortium
Genentech
Information provided by (Responsible Party):
Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00925652
First received: June 19, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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 evaluate the potential additional benefits from participating in an exercise and dietary intervention compared to the dietary intervention alone. 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.


Condition Intervention Phase
Breast Cancer
Drug: Bevacizumab
Drug: Cyclophosphamide
Drug: Methotrexate
Behavioral: Diet Intervention
Behavioral: Diet and Exercise Intervention
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ABCDE: A Phase II Randomized Study of Adjuvant Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Recurrence-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To compare the recurrence-free survival, defined as time on study before local, regional, or distant tumor recurrence, in patients who are randomized to post-neoadjuvant angiogenesis inhibitor therapy compared to those who are randomized to not receive the angiogenesis inhibitor therapy.


Secondary Outcome Measures:
  • Feasibility of bevacizumab and metronomic chemotherapy administration. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    To evaluate the feasibility of bevacizumab and metronomic chemotherapy administration in the adjuvant setting in women with breast cancer previously treated with neoadjuvant chemotherapy or those with node positive triple negative breast cancer.

  • To characterize the side effects and tolerability of bevacizumab and metronomic chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    To characterize the side effects and tolerability of bevacizumab and metronomic chemotherapy in women with residual disease following neoadjuvant chemotherapeutic treatment, or node positive triple negative breast cancer patients after adjuvant chemotherapy.

  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: September 2010
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1. Diet Intervention Arm
The dietary intervention will focus on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber.
Behavioral: Diet Intervention
Series of 13 telephone calls over the course of one-year with a dedicated and trained counselor
Experimental: 2. Diet and exericise intervention arm
The dietary intervention will focus on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients randomized to the diet and exercise groups will also have a target physical activity goal of 180 minutes of moderate-intensity activity each week.
Behavioral: Diet Intervention
Series of 13 telephone calls over the course of one-year with a dedicated and trained counselor
Behavioral: Diet and Exercise Intervention
Counseling targeted toward increasing physical activity and a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.
Experimental: 3. Bevicizumab, CM, and diet intervention
Participants will receive Bevacizumab treatment, cyclophosphamide and methotrexate treatment and well as the dietary intervention that will focus on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber.
Drug: Bevacizumab
Given intravenously once every 3 weeks for approximately 6 months, then every 6 weeks for additional 1.5 years.
Other Name: Avastin
Drug: Cyclophosphamide
Taken orally once a day for approximately 6 months.
Other Name: Cytoxan
Drug: Methotrexate
One pill orally twice a day on days 1 and 2 of each week for approximately 6 months.
Other Name: MTX
Behavioral: Diet Intervention
Series of 13 telephone calls over the course of one-year with a dedicated and trained counselor
Experimental: 4. Bevacizumab, CM, diet and exercise
Participants will receive bevacizumab, cyclophosphamide and methotrexate treatment and well as the dietary intervention that will focus on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber and will also have a target physical activity goal of 180 minutes of moderate-intensity activity each week.
Drug: Bevacizumab
Given intravenously once every 3 weeks for approximately 6 months, then every 6 weeks for additional 1.5 years.
Other Name: Avastin
Drug: Cyclophosphamide
Taken orally once a day for approximately 6 months.
Other Name: Cytoxan
Drug: Methotrexate
One pill orally twice a day on days 1 and 2 of each week for approximately 6 months.
Other Name: MTX
Behavioral: Diet Intervention
Series of 13 telephone calls over the course of one-year with a dedicated and trained counselor
Behavioral: Diet and Exercise Intervention
Counseling targeted toward increasing physical activity and a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.

Detailed Description:
  • Because no one knows which of the study options are 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.
  • Participants assigned to groups 1 or 2 will receive a diet intervention or diet and exercise intervention. They will be seen by the doctor for physical examination every 12 weeks for the first two years during the intervention, and then on an every 6 month basis. Routine laboratory testing will be done at the time of the visits as well. Other blood tests will be done to measure the effect of the diet and exercise interventions at the beginning of the treatment, at 6 months, and at 1 year from the start of the treatment. Additionally, one blood test will be done at the beginning of the treatment to look for hereditary differences in genes related to metabolism.
  • Participants assigned to groups 3 or 4 will undergo the following: Medication: Participants that are placed in the bevacizumab and cyclophosphamide and methotrexate (CM) arm will receive bevacizumab intravenously once every 3 weeks for approximately 6 months, followed by every 6 week treatments for additional 1.5 years; cyclophosphamide orally once a day and methotrexate orally twice a day for the first two days of each week. The treatments with CM therapy and bevacizumab will continue for approximately 6 months. Physical Exams: once 6 weeks of drug therapy (2 cycles)is completed, physical examination frequency is reduced to every 6 weeks (every other cycle) for the additional 6 cycles. Once 24 weeks of drug therapy (8 cycles or about 6 months since the start of therapy) are completed, physical examination will be done every 12 weeks for the duration of protocol therapy. Blood Tests: chemistry and hematology testing will be done prior to start of Cycles 1, 2 and 3 and then every 6 weeks (every other cycle) for the duration of cyclophosphamide and methotrexate chemotherapy. After 24 weeks (8 cycles) of drug treatment, hematology/chemistry testing frequency can be reduced to every 12 weeks (every other cycle) for the rest of bevacizumab treatment. Urine Tests will be done every other cycle for the duration of treatment. Heart function testing by echocardiogram will be done at 6 months, 1, 2, and 3 years after participants start the study. Ultrasound of the blood vessels will be done on those randomized to receive bevacizumab with CM chemotherapy. This test will be done at baseline and after completion of the first and second cycles of therapy.
  • Activities for all Groups: Lifestyle Intervention: All women in this study will complete a number of tests at baseline, 6 and 12 months. Diet Only Group: Participants assigned to this group will be asked to participate in a series of 13 telephone calls over the course of 1 year with. Those assigned to the Diet and Exercize Group (in addition to the information listed above) will receive counseling targeted toward increasing physical activity.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 18 years of age or greater

Exclusion Criteria:

  • 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
  • Serious, non-healing wound, active ulcer, or unhealed bone fracture
  • Known hypersensitivity to any component of bevacizumab or compounds of similar chemical or biologic composition to cyclophosphamide or methotrexate
  • Known HIV infection, as immunosuppression could be worsened by use of cyclophosphamide and methotrexate, and the impact of chemotherapy and/or bevacizumab therapy on the pharmacology of standard anti-HIV therapy is not known
  • Patient may not be pregnant, expect to become pregnant, plan to conceive a child while on study or breastfeeding.
  • Prior history of any malignancy treated without curative intent, or treated with curative intent within the past 5 years. Prior history of DCIS > 5 years before current breast cancer diagnosis is acceptable if ipsilateral (and no radiotherapy given) or contralateral (with or without radiotherapy) or contralateral (with or without radiotherapy). Prior history of contralateral stage 1 breast cancer > 5 years prior to the current breast cancer diagnosis is acceptable, however prior ER/PR+ breast cancer > stage 1 at any time is not allowed.
  • Patients with a pleural effusion or abdominal ascites are excluded because of the theoretical risk for methotrexate accumulation and related toxicity
  • Current use of anticoagulants is allowed as long as patients have been on a stable dose for more than two weeks with stable INR
  • Chronic therapy with full dose aspirin or standard non-steroidal anti-inflammatory agents is allowed
  • While on study, patients may not receive other investigational agents as part of other clinical trials
  • Adjuvant bisphosphonate use, on or off of clinical trial, is allowed. Patients may be started on adjuvant bisphosphonate therapy either before or after ABCDE trial enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00925652

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Indiana
Indiana Unversity Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Faulkner Hospital
Boston, Massachusetts, United States, 02133
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center
Milford, Massachusetts, United States, 01757
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Translational Breast Cancer Research Consortium
Genentech
Investigators
Study Chair: Erica Mayer, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Erica Mayer, MD, MPH, Erica Mayer, M.D., Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00925652     History of Changes
Other Study ID Numbers: 09-134, AVF 4571s; TBCRC 012
Study First Received: June 19, 2009
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
CM
bevacizumab
cyclophosphamide
methotrexate
exercise intervention
diet intervention

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Methotrexate
Bevacizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on July 31, 2014