Status:
UNKNOWN
Chemotherapy With or Without Bevacizumab in Treating Women With Stage I, Stage II, or Stage IIIA Breast Cancer That Can Be Removed By Surgery
Lead Sponsor:
NSABP Foundation Inc
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Breast Cancer
Eligibility:
FEMALE
18-120 years
Phase:
PHASE3
Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination ch...
Detailed Description
OBJECTIVES: Primary * Compare the efficacy of docetaxel followed by doxorubicin hydrocloride and cyclophosphamide (AC) vs docetaxel and capecitabine followed by AC vs docetaxel and gemcitabine hydro...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- The patient must have consented to participate and must have signed and dated an appropriate Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of pre-entry core biopsy material for correlative studies.
- Patients must be female.
- Patients must be 18 years of age or older.
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy.
- The primary breast tumor must be palpable and measure greater than or equal to 2.0 cm on physical exam.
- All patients must have their left ventricular ejection fraction (LVEF) assessed by multigated acquisition (MUGA) scan or echocardiogram within 3 months prior to study entry. The LVEF must be greater than or equal to the lower limit of normal (LLN) for the cardiac imaging facility performing the study. Note: If the cardiac imaging facility cannot provide a LLN, use 50% as the LLN value.
- \- Note: Since the pre-entry LVEF serves as the baseline for comparing subsequent LVEF assessments to determine if bevacizumab therapy can be continued, it is critical that this baseline study be an accurate assessment of the patient's LVEF. If the baseline LVEF is greater than 75%, the investigator should have the study reviewed for accuracy prior to study entry. Following study entry, the LVEF determination may be reviewed up until the time of the post-chemotherapy (preoperative) evaluation. Please note that if a more accurate value is obtained from the review of the baseline MUGA or echocardiogram, the correct value must be submitted to the NSABP before the post-chemotherapy (preoperative) MUGA or echocardiogram is performed or it cannot be used for managing postoperative bevacizumab.
- All patients must have an EKG within 3 months prior to study entry.
- At the time of randomization:
- Absolute neutrophil count (ANC) must be greater than or equal to 1200/mm3.
- Platelet count must be greater than or equal to 100,000/mm3.
- Hemoglobin must be greater than or equal to 10 g/dL.
- There must be evidence of adequate hepatic function by these criteria:
- Total bilirubin must be less than or equal to the ULN for the lab unless the patient has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) resulting from Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and
- Alkaline phosphatase must be less than or equal 2.5 x ULN for the lab; and
- Aspartate Aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab.
- Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal 2.5 x ULN, then the AST must be less than or equal the ULN. If the AST is greater than the ULN but less than or equal 1.5 x ULN, then the alkaline phosphatase must be less than or equal ULN.
- Patients with either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal 2.5 x ULN are eligible for inclusion in the study if bone scans do not demonstrate metastatic disease. Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy.
- Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in the study if liver imaging does not demonstrate metastatic disease and adequate bone marrow and liver function results as described above are met.
- The following criteria for evidence of adequate renal function must be met:
- Serum creatinine less than or equal ULN for the lab.
- Calculated creatinine clearance must be greater than 50 mL/min.
- Urine protein/urine creatinine (UPC) ratio must be less than 1.0.
- Patient must be able to swallow oral medications.
- Exclusion criteria:
- Tumor determined to be strongly human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification).
- Excisional or incisional biopsy for this primary breast tumor.
- Surgical axillary staging procedure prior to study entry. Exceptions: 1) Fine Needle Aspiration (FNA) or core biopsy of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted.
- Tumors clinically staged as T4.
- Ipsilateral cN2b or cN3 disease. (Patients with cN1 or cN2a disease are eligible.)
- Definitive clinical or radiologic evidence of metastatic disease.
- Synchronous bilateral breast cancer (invasive or DCIS).
- Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry.
- Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. (These patients are eligible if this therapy is discontinued prior to randomization.)
- Therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulator (SERM), either for osteoporosis or breast cancer prevention. (Patients are eligible only if these medications are discontinued prior to randomization.)
- Prior history of breast cancer, including DCIS. (Patients with a history of lobular carcinoma in situ \[LCIS\] are eligible.)
- Prior therapy with anthracyclines, taxanes, capecitabine, 5-FU (fluorouracil), gemcitabine, or bevacizumab for any malignancy.
- Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization and is deemed by her physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
- Cardiac disease that would preclude the use of anthracyclines. This includes:
- angina pectoris that requires the use of anti-anginal medication;
- history of documented congestive heart failure;
- serious cardiac arrhythmia requiring medication;
- severe conduction abnormality;
- valvular disease with documented cardiac function compromise; and
- uncontrolled hypertension defined as BP greater than 150/90 on antihypertensive therapy. (Patients with hypertension that is well controlled on medication are eligible.)
- History of myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function.
- History of transient ischemic attack (TIA) or cerebrovascular accident (CVA).
- History of other arterial thrombotic event within 12 months before study entry.
- Symptomatic peripheral vascular disease.
- Any significant non-traumatic bleeding within 6 months before study entry.
- Serious or non-healing wound, skin ulcers, or incompletely healed bone fracture.
- Gastroduodenal ulcer(s) determined by endoscopy to be active.
- Invasive procedures defined as follows:
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to planned start of study therapy. (Note: Placement of a vascular access device is not considered a major surgical procedure.)
- Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of the study.
- Known bleeding diathesis or coagulopathy. (Patients on warfarin with an in-range international normalized ratio \[INR\] \[usually between 2 and 3\] are eligible.)
- Sensory/motor neuropathy greater than or equal grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE v3.0).
- Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude treatment with any of the treatment regimens or would prevent required follow-up.
- Conditions that would prohibit administration of corticosteroids.
- History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.
- Administration of any investigational agents within 30 days before study entry.
- Pregnancy or lactation at the time of proposed randomization.
Exclusion
Key Trial Info
Start Date :
November 1 2006
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2018
Estimated Enrollment :
1206 Patients enrolled
Trial Details
Trial ID
NCT00408408
Start Date
November 1 2006
End Date
March 1 2018
Last Update
September 18 2017
Active Locations (442)
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1
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
2
East Bay Radiation Oncology Center
Castro Valley, California, United States, 94546
3
Eden Medical Center
Castro Valley, California, United States, 94546
4
Valley Medical Oncology Consultants - Castro Valley
Castro Valley, California, United States, 94546