Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer
Phase: Phase 2
Diagnosis: Breast: Early Stage Disease
NCT ID: NCT00925652
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 09-134
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.
Dana-Farber Cancer Institute, Beth-Israel Deaconess Medical Center, Brigham and Women's Hospital
Erica Mayer, MD,
Dana-Farber Cancer Institute
Steven Come, MD,
Beth Israel Deaconess Medical Center
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
Dana-Farber Cancer Institute:
Breast Cancer Nursing Team, 617-632-3478
- Histologically or cytologically confirmed invasive breast cancer. HER2 positive
disease is not allowed.
- If tumor is triple negative (ER-/PR-/HER2-), tumor may be clinical stage I-III
pre-operatively, per AJCC 6th edition, based on baseline evaluation by clinical
examination and/or breast imaging.
- If tumor is hormone receptor positive, tumor must be clinical stage III
preoperatively, per AJCC 6th edition, based on baseline evaluation by clinical
examination and/or breast imaging, or pathologic stage IIB or greater at time of
- Patients must have completed preoperative (neoadjuvant) chemotherapy containing an
anthracycline, a taxane, or both. Patients must have received preoperative therapy as
part of a clinical trial are acceptable.
Protocol therapy must be initiated 180 days or less after last surgery for breast cancer.
- 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
- 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
- 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 abscence of symptoms
- Prior history of hypertensive crisis or hypertensive encephalopathy
- History if myocardial infarction or unstable angina within 12 months prior to
- 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
- 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
- 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
- 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