Neoadjuvant Treatment of Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Doxorubicin; Cyclophosphamide; Carboplatin; Nab-paclitaxel; GM-CSF; Trastuzumab; Bevacizumab
Intervention description: 60 mg/m2 IV, bolus once a day every 14 days x 2-4 cycles; 600 mg/m2 IV once a day every 14 days x 2-4 cycles; AUC 2 IV weekly for 9-12 doses beginning two weeks after completion of last AC dose; 100 mg/m2 IV over 30 min weekly for 9-12 doses beginning two weeks after completion of last AC dose; 250 μg/mL IV or on day 4-13 of each subcutaneous cycle of doxorubicin and injection cyclophosphamide; 4mg/kg, and then2 mg/kg q wk IV weekly for 12-16 doses beginning two weeks after completion of last AC dose; 10mg/kg q 2 wks
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Cyclophosphamide; Bevacizumab; Carboplatin; Doxorubicin; Trastuzumab; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Inflammatory; Breast Cancer; Female; Neo-adjuvant; HER-2 positive; Hormone receptor

Summary:

      Study Aims

        1. To measure the clinic response rates in patients with breast cancer more than 2 cm
           and/or lymph node positive breast cancer treated with 2-4 cycles of biweekly
           doxorubicin, cyclophosphamide with Granulocyte-macrophage colony-stimulating factor
           (GM-CSF) (days 4-13) followed by weekly carboplatin/nab-paclitaxel given for 3 weeks,
           followed by 1 week of rest, for a total of 9-12 doses. (Her-2 positive patients, in
           addition, will receive Trastuzumab weekly (12-16 doses) and Her-2 negative patients will
           receive Bevacizumab (6-8 doses) q 2 weeks).

        2. To measure the microscopic pathological response rate of this regimen.

        3. To measure toxicity and the delivered dose intensity of this regimen.

        4. To assess the association between microscopic pathologic complete response and clinical
           complete response at the primary tumor site in these patients.

        5. To determine whether the GM-CSF increases the post treatment dendritic cells (S100+)
           percentage in the tumor draining lymph node as compared to pretreatment S100+ cells.

        6. To determine whether the patients with a higher percent S100+ have a better clinical,
           pathological response, Disease Free Survival (DFS), and overall Survival (OS).

        7. To determine whether flow cytometry of dendritic cells performed post-treatment in blood
           sample shows an increase in dendritic cell population compared to pretreatment levels.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be women with a histologically confirmed diagnosis of breast cancer that
             is more than 2 cm and/or lymph node positive. Histologic confirmation shall be by
             either core needle biopsy or incisional biopsy. Punch biopsy is allowed if invasive
             breast cancer is documented.

          -  Patients must meet one of the criteria defined below (indicate one):

               1. Selected Stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0) disease judged primarily
                  unresectable by an experienced breast surgeon; or otherwise deemed - appropriate
                  candidates for neoadjuvant treatment.

               2. Stage IIIB (T4, Any N, M0) or (Any T, N3, M0) disease.

          -  Physical examination, chest x-ray and any x-rays or scans needed for tumor assessment
             must be performed within 90 days prior to registration.

          -  All patients must have a multiple gated acquisition (MUGA) scan or echocardiogram scan
             performed within 90 days prior to registration and left ventricular ejection fraction
             (LVEF) percentage must be greater than the institutional lower limit of normal.

          -  Patients must have a serum creatinine and bilirubin ≤ the institutional upper limit of
             normal, and an serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate
             pyruvate transaminase (SGPT) ≤ 2x the institutional upper limit of normal. These tests
             must have been performed within 90 days prior to registration.

          -  Patients must have an absolute neutrophil count (ANC) of ≥ 1,500/μl and a platelet
             count of ≥ 100,000/μl. These tests must have been performed within 90 days prior to
             registration.

          -  Patients must have a performance status of 0-2 by Zubrod criteria

          -  In calculating days of tests and measurements, the day a test or measurement is done
             is considered Day 0. Therefore, if a test is done on a Monday, the Monday four weeks
             later would be considered Day 28. This allows for efficient patient scheduling without
             exceeding the guidelines. If Day 28 or 42 falls on a weekend or holiday, the limit may
             be extended to the next working day.

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines.

        Exclusion Criteria:

          -  Patients with the clinical diagnosis of congestive heart failure or angina pectoris
             are NOT eligible.

          -  Pregnant or nursing women may not participate due to the possibility of fetal harm or
             of harm to nursing infants from this treatment regimen. Women of reproductive
             potential may not participate unless they have agreed to use an effective
             contraceptive method. A urine pregnancy test is required for women of childbearing
             potential.