Paclitaxel With or Without Carboplatin and/or Bevacizumab Followed by Doxorubicin and Cyclophosphamide in Treating Patients With Breast Cancer That Can Be Removed by Surgery
Condition: Male Breast Carcinoma; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma
MeSH terms: Carcinoma; Breast Neoplasms; Breast Neoplasms, Male
Intervention: Bevacizumab; Carboplatin; Cyclophosphamide; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Paclitaxel
Intervention description: Given IV; Given IV; Given IV; Given IV; Correlative studies; Given IV
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Bevacizumab; Carboplatin; Doxorubicin; Liposomal doxorubicin; Albumin-Bound Paclitaxel; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G; Endothelial Growth Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 454.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or
      bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with
      breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel,
      carboplatin, 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. Bevacizumab may
      stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy
      together with bevacizumab before surgery may make the tumor smaller and reduce the amount of
      normal tissue that needs to be removed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Invasive breast cancer, diagnosed by core needle or incisional biopsy (excisional
             biopsy not permitted)

          -  The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor
             (ER) and progesterone receptor (PgR) negative or staining present in =< 10% of
             invasive cancer cells by immunohistochemistry (IHC)

          -  The invasive tumor must be HER2-negative, defined as IHC 0-1+ or with a fluorescent in
             situ hybridization (FISH) ratio (HER2 gene copy/chromosome 17) of < 2.0 if IHC 2+

          -  Clinical stage II-III invasive breast cancer with intent to perform surgical resection
             after neoadjuvant therapy; patients with inflammatory breast cancer are not eligible;
             staging to rule out metastatic disease is recommended for clinical stage III patients

          -  Patients with multicentric or bilateral disease are eligible if the target lesion
             meets eligibility criteria

          -  Patient agrees to undergo pretreatment research biopsies

          -  No prior chemotherapy, hormone therapy, or radiation therapy with therapeutic intent
             for this cancer

          -  The target lesion in the breast must be >= 1 cm, clinically or radiographically;
             palpable or radiographically measurable axillary adenopathy will be recorded but will
             not serve as measurable disease for the primary endpoint; patients with axillary
             disease only (no identifiable tumor in the breast that is >= 1 cm on physical exam or
             radiographic study) are not eligible to participate

          -  Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or
             lower gastrointestinal [GI] bleeding) within 6 months of registration are not eligible

          -  No serious or non-healing wound, skin ulcers or bone fracture; no abdominal fistula,
             gastrointestinal perforation or intra-abdominal abscess within the past 6 months; no
             major surgical procedure within 28 days prior to randomization or anticipation of need
             for major surgery during the course of study

          -  The following are not considered to be major surgical procedures that would be
             prohibited in the 28 days prior to, or following study randomization: obtaining the
             required research needle biopsies; placement of a radiopaque clip to localize a tumor
             or tumors for subsequent surgical resection; placement of a port for central venous
             access; fine needle aspiration of a prominent or suspicious axillary lymph node;
             needle biopsy of a clinically or radiographically detected lesion to rule out
             metastatic disease; or pretreatment sentinel lymph node sampling

          -  No baseline neuropathy grade >= 2

          -  Zubrod performance status 0-1

          -  Pregnant or nursing women are not eligible; all women of reproductive potential must
             have a negative pregnancy test at baseline and agree to use an effective, non-hormonal
             method of contraception during the entire period of treatment on the study

          -  Patients with congestive heart failure are not eligible, nor are patients with
             myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke
             or transient ischemia attack (TIA) within the past 12 months, uncontrolled
             hypertension (systolic blood pressure [SBP] > 160 or diastolic blood pressure [DBP] >
             90), uncontrolled or symptomatic arrhythmia, or grade II or greater peripheral
             vascular disease

          -  Patients must have a pretreatment multi gated acquisition (MUGA) scan or
             echocardiogram with a left ventricular ejection fraction (LVEF) above the
             institutional lower limit of normal

          -  Granulocytes > 1,000/mcl

          -  Platelets > 100,000/mcl

          -  Total bilirubin =< 1.5 x upper limits of normal

          -  Calculated or measured > 30 ml/min

          -  Urine protein =< 1+ or urine protein to creatinine (UPC) ratio < 1

               -  Patients discovered to have >= 2+ proteinuria at baseline must undergo a 24-hour
                  urine collection that must demonstrate < 1 g of protein/24 hr, or UPC ratio < 1
                  to allow participation in the study

          -  Serum alanine aminotransferase (ALT) =< 2.5 x upper limits of normal

          -  Serum beta human chorionic gonadotropin (HCG) negative (for women of child bearing
             potential)

          -  Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x upper limit of
             normal (ULN)

               -  Unless patient is on therapeutic doses of warfarin; if so, the patient must have
                  an INR =< 3 on a stable dose of warfarin, must have not active bleeding or
                  pathologic condition that is associated with a high risk of bleeding