The primary objective of this study is to compare the safety of dose-dense Abraxane 260
mg/m^2 or Taxol 175 mg/m^2 given every 2 weeks following dose-dense AC chemotherapy.
Bevacizumab will be administered at 10 mg/kg every 2 weeks throughout chemotherapy, and then
at 15 mg/kg every 3 weeks following chemotherapy.
Inclusion Criteria:
A patient will be eligible for inclusion in this study only if all of the following
criteria are met:
- Females, age greater than or equal to 18 to less than or equal to 70 years old.
- ER and PR status have been determined.
- Operable, histologically confirmed adenocarcinoma of the breast
- Must meet 1 of the following criteria:
- T1-3, N1-3, M0, regardless of ER or PR status.
- T > 2 cm, N0, M0 (T2-3N0M0), regardless of ER or PR status.
- T > 1 cm, N0, M0, ER or PR positive and grade 3
- Patients with one sentinel lymph node metastasis 0. 2-2 mm in size are not required
to undergo completion axillary dissection unless only 1 sentinel lymph node was
examined. This completion axillary dissection is optional if 1 out of 2 or more
sentinel lymph nodes is positive for a micrometastasis. Therefore if 1 of 1 sentinel
lymph node is positive for micrometastasis(0. 2-2 mm), then a completion axillary
dissection is required.
- Patients with more than one sentinel node micrometastasis or 1 node with a
micrometastasis > 2 mm and/or T3 disease must undergo completion, standard axillary
dissection.
- Note: the following are not eligible-
T1b,c,N0M0 and ER or PR positive and grade 1 or 2 Tx tumors (regardless of nodal status) T4
disease [i. e., patients with fixed tumor, peau d'orange skin changes, skin ulcerations, or
inflammatory changes
- Note: Sentinel lymph node micrometastasis < 0. 2 mm in considered N0 disease
- Negative surgical margins on lumpectomy or mastectomy specimen (no ink on invasive
cancer and no ink on DCIS).
- ECOG performance status 0-1
- Normal ECG (as assessed by the investigator).
- No pre-existing peripheral neuropathy.
- It has not been longer than 84 days since the date of definitive surgery (eg,
mastectomy or in the case of a breast-sparing procedure, axillary dissection).
- Laboratory values must be as follows:
- White blood cell count: > or equal to 3,000/mm^3
- Absolute neutrophil count:> or equal to 1,500/mm^3
- Platelets:> or equal to 100,000/mm^3
- Hemoglobin: > or equal to 8g/dL
- Bilirubin:< or equal to the institution's ULN
- Cretinine: < or equal to 1. 7 mg/dL
- AST and ALT and alkaline phosphatase may be up to 2. 5 x institutional.
- All staging studies including physical exam, chest x-ray, and bone scan must show no
evidence of metastatic disease, including suspicious lymphadenopathy or skin nodules
on physical exam. A chest x-ray and bone scan are mandatory; however, all other
staging studies are at the treating physician's discretion. Any other staging test
(eg, CT scans, MRI studies, ultrasound of abdomen, PET scans) must be negative for
metastatic disease. An abdominal CT scan or PET scan is mandatory for patients with
liver function tests elevated above the ULN to rule out metastic disease. If the
patient has a stafing PET scan then a bone scan is not necessary, but a chest x-ray is
required.
- Patient has a negative serum pregnancy test < or equal to 14 days of the first dose of
study drug (patients of childbearding potential).
- If fertile, patient has agreed to us an acceptable method of birth control to avoid
pregnancy [Note: oral contraceptives are not allowed] for the chemotherapy and
hormonal therapy and for 6 months thereafter.
- If obese, a patient must be treated with doses calculated using his/her actual BSA
(the physician must be comfortable treating at the full BSA dose regardless of BSA).
- Patient has signed a Patient Informed Consent Form.
Exclusion Criteria:
A patient will not be eligible for inclusion in this study if any of the following criteria
apply:
- Patinets with HER-2 positive breast cancer (IHC 3+ or FISH +) who are eligible for
adjuvant Herceptin therapy.
- Stage IV breast cancer (M1 disease on TNM staging system).
- Prior anthracycline, anthracenedione (mitoxantrone), or taxane therapy
- Neoadjuvant therapy for this breast cancer.
- Previous invasive cancers if treated < 5 years prior to entering this study, except
basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; the
latter are not required to have occurred more than 5 years prior to study entry.
- Prior invasive breast cancer if diagnosed < 5 years prior to entering study. Patients
must have finished adjuvant hormonal therapy prior registration. Patients with prior
DCIS are eligible. Patients with DCIS who were treated with tamoxifen must have
finished tamoxifen prior to registration.
- Serious medical illness, other than that treated by this study, which would limit
survival to < 4 years, or psychiatric condition that would prevent informed consent
and compliance with study treatment.
- Uncontrolled or severe cardiovascular disease including recent (< or equal to 12
months)
- Active uncontrolled bacterial, viral (including clinically defined AIDS), or fungal
infection
- Patients with active or chronice hepatitis with abnormal LFTs or patients who are
known to be HIV positive.
- Uncontrolled disease such as uncontrolled diabetes.
- Any Prior history of hypertensive crisis or hypertensive encephalopathy.
- Any known CNS disease.
- Known hypersensitivity to any component of bevacizumab.
- No history of cerebrovascular accident or transient ishemic attack at any time
- Active symptomatic vascular disease, e. g.aortic aneurysm or aortic dissection, an no
peripheral vascular disease, e. g. claudication, within six months of study entry.
- No major surgical procedure, open biopsy, or significant traumatic injury within 28
days and no core biopsy or minnor surgical procedure (excluding placement of a
vascular access device) within seven days of study entry. No anticipated need for
major surgical procedure during the course of study - No history of abdominal fistula,
gastronial perforation, or intra- abdominal process within six months of study entry.
- No serious non-healing wound, ulcer, or bone fracture
- No proteinuria at screening as demonstrated by urine protein: urine creatinine (UPS)
ratio of > or equal to 1. 0 or urine dipstick for proteinuria > or equal to 2+
(patients discovered to have > or equal to 2+ proteinuria on dipstick urinalysis at
baseline should undergo a 24 hour urnie collection and must demonstrate < or equal to
1g or protein in 24 hours to be eligible).
- Inadequately controlled hypertension (definded as systolic blood pressure > 150 mmHg
and /or diastolic blood pressure> 100 mmHg on antihypertensive medications) or NYHA
Grade 2 or greater congestive heart failure.
- History or coagulopathy, bleeding diathesis, therapeutic anti coagulation other than
low dose or chronic ASA > or equal to 325 mg per day. Low dode coumadin for
anticoagulation of venous access device or low dose molecular weight heparin (LMWH)
for deep vein thrombosis prophylaxis or low dose (325 mg or less) ASA prophylaxis are
allowed, but are best avoided if the treating physician feels it is safe to do so.
- LVEF on cardiac ECHO < 50% (or institutional LLN)and > or equal to 70%
- Patients receiving concurrent immunotherapy.
- A history of other malignancy within the last 5 years, which could affect the
diagnosis or assessment of breast cancer recurrence or which could shorten a patient's
survival
- Patient has had an organ allograft
- Patient is pregnant or breastfeeding
- Patient is unable to comply with requirments of study
- Patient is recieving any other investigational drugs
Birmingham, Alabama 35205, United States
Sedona, Arizona 86336, United States
Denver, Colorado 80220, United States
Torrington, Connecticut 06790, United States
Indianapolis, Indiana 46227, United States
Minneapolis, Minnesota 55404, United States
Columbia, Missouri 65201, United States
St. Louis, Missouri 63136, United States
Henderson, Nevada 89052, United States
Raleigh, North Carolina 27607, United States
Eugene, Oregon 97401, United States
Greenville, South Carolina 29615, United States
Fort Worth, Texas 76104, United States
Fredericksburg, Texas 78624, United States
Dallas, Texas 75231, United States
Tyler, Texas 75702, United States
Houston, Texas 77024, United States
McAllen, Texas 78503, United States
Bedford, Texas 76022, United States
Longview, Texas 75601, United States
El Paso, Texas 79915, United States
Austin, Texas 78731, United States
Dallas, Texas 75246, United States
Waco, Texas 76712, United States
Norfolk, Virginia 23502, United States
Fairfax, Virginia 22031, United States
Vancouver, Washington 98684, United States
