| City: |
|
Boston |
|
State:
|
|
MA |
| Zip Code: |
|
02133 |
| Conditions: |
|
Breast Cancer |
| 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 breast, 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 summary: |
|
- 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 year on study, and then on an every 6 month basis. Routine
laboratory testing will be done at the discretion of the study doctor. Other blood
tests will be done to measure the effect of the diet and exercise interventions at the
beginning of the treatment, every 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 12
months; 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. Each cycle of treatment lasts three weeks.
Physical Exams: Physical exams will be done at the beginning of each cycle for the
first 12 weeks. Once the participant has completed 12 weeks of protocol therapy, they
may be seen for physical examination by the study doctor every 6 weeks for the duration
of the study. Blood Tests: Chemistry and hematology testing will be done at the
beginning of each cycle of treatment while participants are receiving CM chemotherapy.
After 9 cycles, chemistry and hematology blood tests will be done every other cycle
during the following 8 cycles and at the end of treatment with bevacizumab. 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 year, and 2 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. |
| Criteria: |
|
Inclusion Criteria:
- 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
definitive surgery.
- 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 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 abscence 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 |
|
|
|
| Study is available at: |
|
Faulkner Hospital
Boston, MA 02133
United States
Primary Contact:
Erica Mayer, MD
Phone: 617-632-3800 |
|
|
If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
|
| Trials Alerts: |
|
If you would like to be
notified of new clinical trials as they become available please
register for a free account.
|
|
| Data Source: |
|
ClinicalTrials.gov |
| Date Processed: |
|
March 23, 2011 |
Modifications to
this listing: |
|
Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
|
|
|
|
|
|
|
|