Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: carboplatin; paclitaxel albumin-stabilized nanoparticle formulation; vorinostat; placebo
Intervention description: Given IV; Given IV; Given orally; Given orally
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 68.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; ductal breast carcinoma; lobular breast carcinoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel albumin-stabilized
      nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Vorinostat may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help
      carboplatin and paclitaxel albumin-stabilized nanoparticle formulation work better by making
      tumor cells more sensitive to the drugs. Giving chemotherapy with or without vorinostat
      before surgery may make the tumor smaller and reduce the amount of normal tissue that needs
      to be removed.

      PURPOSE: This randomized phase II trial is studying how well giving carboplatin together with
      paclitaxel albumin-stabilized nanoparticle formulation works with or without vorinostat in
      treating women with breast cancer that can be removed by surgery.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed infiltrating ductal breast cancer by core needle biopsy

               -  Mixed ductal and lobular disease allowed

               -  Infiltrating lobular cancer allowed in the run-in portion only

          -  Unresected, clinically measurable disease, meeting 1 of the following clinical staging
             criteria:

               -  T2, T3, or T4 lesion, any N, M0

               -  T1c, N1-3,M0

          -  Patients with skin metastases to the ipsilateral breast for whom chemotherapy is
             planned prior to definitive surgery are eligible for the primary study portion

          -  HER2-negative disease

          -  Hormone receptor status* meeting 1 of the following criteria:

               -  Estrogen receptor (ER)-negative and progesterone receptor (PR)-negative

               -  ER-positive (grade II or III) and PR-positive or PR-negative NOTE: *Any ER or PR
                  status for the run-in portion

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-1

          -  Menopausal status not specified

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 150,000/mm³

          -  Hemoglobin ≥ 9 g/dL

          -  Creatinine ≤ 1.5 times the upper limit of normal (ULN)

          -  Creatinine clearance ≥ 50 mL/min

          -  Total bilirubin normal

          -  AST(SGOT) and ALT(SGPT) ≤ 2.5 times (ULN)

          -  alkaline phosphatase ≤ 2.5 times ULN

          -  PT such that INR ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is
             on a stable dose of therapeutic warfarin) and PTT ≤ ULN

          -  Adequate cardiac function defined as no evidence of PR prolongation or AV block on
             baseline electrocardiogram (ECG)

          -  Willing to use effective, non-hormonal contraception while on treatment and for at
             least 3 months thereafter

          -  Not pregnant or nursing

          -  No pre-existing peripheral neuropathy ≥ grade 2

          -  No history of severe hypersensitivity reaction to any drug formulated with polysorbate
             80 or to E. coli-derived products

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to vorinostat

          -  No medical condition which, in the opinion of the investigator, puts the patient at
             risk of potentially serious complications while on this therapy

        PRIOR CONCURRENT THERAPY:

          -  At least 4 weeks since prior valproic acid or other histone deacetylase inhibitor

          -  No prior chemotherapy, radiotherapy, or endocrine therapy for this cancer

               -  Prior tamoxifen or raloxifene or another agent for prevention of breast cancer
                  allowed as long as the patient has discontinued the treatment ≥ 1 month prior to
                  baseline study biopsy

          -  No systemic treatment for prior cancer within the past 5 years (primary study portion)

          -  No prior or ongoing systemic treatment for this cancer (primary study portion)

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent histone deacetylase inhibitor

          -  No other concurrent chemotherapy, antiestrogen therapy, radiotherapy, or other
             investigational systemic therapy

          -  No other concurrent biologic therapy

          -  No other concurrent investigational drugs