Clinical trial NCT00408408 (phase 3, status: unknown status)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: capecitabine, cyclophosphamide, docetaxel, doxorubicin hydrochloride (adriamycin), gemcitabine hydrochloride
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, ClCCN(CCCl)P1(=O)NCCCO1, [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O, NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
Eligibility criteria:

        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.