S0800, Nab-Paclitaxel, Doxorubicin, Cyclophosphamide, and Pegfilgrastim With or Without Bevacizumab in Treating Women With Inflammatory or Locally Advanced Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: bevacizumab; pegfilgrastim; cyclophosphamide; doxorubicin hydrochloride; paclitaxel albumin-stabilized nanoparticle formulation
Intervention description: Given IV; Given subcutaneously; Given IV; Given IV; Given IV
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Bevacizumab; Doxorubicin; Liposomal doxorubicin; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 215.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: inflammatory breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; HER2-negative breast cancer; estrogen receptor-negative breast cancer; estrogen receptor-positive breast cancer; progesterone receptor-negative breast cancer; progesterone receptor-positive breast cancer; stage IIIC breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle
      formulation, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of
      tumor cells, either by killing the cells or by stopping them from dividing.
      Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells
      found in bone marrow or peripheral blood and may help the immune system recover from the side
      effects of chemotherapy. Monoclonal antibodies, such as bevacizumab, can block tumor growth
      in different ways. Some find tumor cells and kill them or carry tumor-killing substances to
      them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may
      also may stop the growth of tumor cells by blocking blood flow to the tumor. Giving these
      treatments before surgery may make the tumor smaller and reduce the amount of normal tissue
      that needs to be removed. It is not yet known which treatment regimen is more effective in
      treating women with breast cancer.

      PURPOSE: This randomized phase II trial is studying paclitaxel albumin-stabilized
      nanoparticle formulation, doxorubicin, cyclophosphamide, and pegfilgrastim to compare how
      well they work when given with or without bevacizumab in treating women with inflammatory or
      locally advanced breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically or pathologically confirmed breast cancer meeting one of the following
             criteria:

               -  Locally advanced disease (stage IIIB disease, stage IIB/IIIA, or stage IIIC
                  disease)

               -  Inflammatory disease meeting the following two clinicopathologic criteria:

                    -  Diffuse erythema AND edema (peau d'orange) of the breast involving the
                       majority of the skin of the breast, i.e., more than 50%

                    -  A biopsy demonstrating cancer either within the dermal lymphatics OR in the
                       breast parenchyma itself

          -  HER2/neu-negative tumor as demonstrated by 0 or 1+ (weak or no staining) by DAKO, IHC,
             or equivalent test OR no gene amplification by FISH*

               -  2+ by DAKO or IHC allowed provided FISH* negative

          -  NOTE: *A negative FISH test ratio is < 1.8 or FISH HER2 gene copy < 4.0; if only a
             positive or negative result is available from the FISH test, a negative result is
             acceptable for study entry

          -  Hormone receptor status known

        PATIENT CHARACTERISTICS:

          -  Menopausal status not specified

          -  Zubrod performance status 0-2

          -  Granulocyte count > 1,500/mm^3

          -  ANC ≥ 1,500/mm^3

          -  Platelet count > 100,000/mm^3

          -  Hemoglobin 9.0 g/dL

          -  Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

          -  Bilirubin ≤ 1.5 mg/dL

          -  ALT and AST ≤ 3 times ULN

          -  Alkaline phosphatase ≤ 2.5 ULN (unless bone metastasis is present in the absence of
             liver metastasis)

          -  Urine protein:creatinine ratio ≤ 0.5 OR urine protein < 1,000 mg on 24-hour urine
             collection

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Able to take oral medications (e.g., no uncontrolled nausea, vomiting, or diarrhea,
             lack of physical integrity of the upper gastrointestinal tract, or malabsorption
             syndrome)

          -  QTc < 500 msec by EKG

          -  LVEF normal by MUGA or ECHO (for patients with hypertension or for patients > 60 years
             of age)

          -  NYHA class II cardiac function by baseline ECHO/MUGA (for patients who have received
             central thoracic radiotherapy that included the heart in the radiotherapy port, or for
             patients who have a history of class II heart failure but are asymptomatic on
             treatment are eligible)

          -  No history of stroke (cerebrovascular accident), transient ischemic attack, or cardiac
             event within the past 12 months, including any of the following:

               -  Myocardial infarction (including severe/unstable angina)

               -  Coronary/peripheral artery bypass graft

               -  Symptomatic congestive heart failure

               -  Pulmonary embolism

          -  No poorly controlled hypertension, defined as recurrent or persistent (≥ 24 hours)
             elevated blood pressure (i.e., systolic blood pressure ≥ 140 mm Hg and/or diastolic
             blood pressure ≥ 90 mm Hg)

          -  No other malignancy within the past 5 years except for adequately treated basal cell
             or squamous cell skin cancer or in situ cervical cancer

          -  Peripheral neuropathy < grade 2

        PRIOR CONCURRENT THERAPY:

          -  No prior tyrosine kinase inhibitors

          -  More than 5 years since prior chemotherapy, radiotherapy, or biologic therapy (e.g.,
             trastuzumab or bevacizumab) for invasive breast cancer

          -  At least 7 days since prior hormonal therapy

          -  At least 7 days since prior and no concurrent strong CYP3A4 inhibitors (e.g.,
             ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone,
             nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) or grapefruit juice

          -  No concurrent CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine,
             rifampin, rifabutin, rifapentin, phenobarbital, St. John's wort)

          -  No other concurrent therapy for the treatment of breast cancer except for
             bisphosphonates

          -  No concurrent brachytherapy