Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III Breast Cancer
Condition: Estrogen Receptor-negative Breast Cancer; HER2-negative Breast Cancer; Progesterone Receptor-negative Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms
Intervention: pegylated liposomal doxorubicin hydrochloride; epirubicin hydrochloride; carboplatin; therapeutic conventional surgery; paclitaxel; laboratory biomarker analysis; quality-of-life assessment
Intervention description: Given IV; Given IV; Given IV; Undergo definitive surgery; Given IV; Correlative studies; Ancillary studies
Intervention MeSH terms: Paclitaxel; Carboplatin; Doxorubicin; Liposomal doxorubicin; Epirubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pegylated liposomal doxorubicin hydrochloride and
      carboplatin followed by surgery and paclitaxel work in treating patients with stage II-III
      breast cancer that does not have estrogen receptors, progesterone receptors, or large amounts
      of human epidermal growth factor receptor 2 (HER2)/neu protein (triple negative). Drugs used
      in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, carboplatin, and
      paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. Giving pegylated
      liposomal doxorubicin hydrochloride and carboplatin before surgery may make the tumor smaller
      and reduce the amount of normal tissue that needs to be removed. Giving pegylated liposomal
      doxorubicin hydrochloride and carboplatin followed by surgery and paclitaxel may be an
      effective treatment for breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women with previously untreated, unilateral stage II-III breast cancer, ER/PgR/HER2
             negative (ER =< 5%, PgR =< 5%, HER2 0-1+ by immunohistochemistry [IHC] or fluorescence
             in situ hybridization [FISH] =< 2.0); if clinically negative lymph nodes, tumor size
             should be minimum 1.0 cm and identifiable under office-based ultrasound guidance

          -  Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at
             screening for patients of child-bearing potential within one week prior to enrollment

          -  Patients with reproductive potential must use an adequate contraceptive method (e.g.
             abstinence, intrauterine device, oral contraceptives, barrier device with spermicide
             or surgical sterilization) during treatment and for three months after completing
             treatment

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status < 2

          -  Life expectancy >= 52 weeks excluding their diagnosis of breast cancer

          -  Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

          -  Platelets >= 100,000 cells/mm^3

          -  Hemoglobin > 9.0 g/dL

          -  Creatinine < 2.5 mg/dL

          -  Total bilirubin < 1.5 X upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2.5 X institutional ULN

          -  Patients must have normal cardiac function, as evidenced by a left ventricular
             ejection fraction (LVEF) within institutional normal limits; echocardiogram may be
             used if multi gated acquisition (MUGA) scan is not available, but the same test must
             be used throughout the study to evaluate LVEF

          -  Computed tomography of the chest, abdomen, and pelvis (CT CAP) and bone scan performed
             within 30 days prior to study entry and does not demonstrate metastatic disease

          -  Patients may not receive concurrent treatment with other investigational or commercial
             agent(s) for treatment of their breast cancer

          -  The patient or, if applicable, her legally authorized representative must have signed
             and dated an Institutional Review Board (IRB)-approved consent form that conforms to
             federal and institutional guidelines

          -  Patients must be eligible to undergo surgery, either lumpectomy or mastectomy for
             local treatment of the breast cancer; surgical margins at discretion of surgeon per
             National Comprehensive Cancer Network (NCCN) guidelines; axillary exploration at
             discretion of surgeon but all patients minimally have sentinel lymph node evaluation
             at time of surgery

          -  Imaging by magnetic resonance imaging (MRI), ultrasound and/or mammogram and physical
             exam to document lesions size must be performed within 30 days of study entry

          -  Must not exhibit a non-healing wound or any skin breakdown

          -  Before administering liposomal doxorubicin, patients must wait 4-6 weeks after surgery

          -  Submission of tumor samples from the diagnostic biopsy and breast surgery is required
             for all patients

        Exclusion Criteria:

          -  Women who are pregnant or breastfeeding

          -  Second primary malignancy except most situ carcinoma (e.g. in situ carcinoma of the
             cervix, adequately treated non-melanomatous carcinoma of the skin) or other malignancy
             treated at least 5 years previously with no evidence of recurrence

          -  Definitive clinical or radiologic evidence of metastatic disease; imaging must have
             been performed no greater than 30 days prior to initiation of chemotherapy

          -  Diagnosis of inflammatory breast cancer

          -  History of hypersensitivity reactions attributed to a conventional formulation of
             doxorubicin hydrochloride (HCL) or the components of doxil, paclitaxel, or carboplatin

          -  Serious concomitant systemic disorders (including active infections or chronic
             infection requiring suppressive antibiotics) that would compromise the safety of the
             patient or compromise the patient's ability to complete the study, at the discretion
             of the investigator

          -  Myocardial infarct or unstable angina within 6 months before enrollment, New York
             Heart Association (NYHA) class II or greater heart failure, uncontrolled angina,
             severe uncontrolled ventricular arrhythmias, clinically significant pericardial
             disease, valvular disease with documented compromise in cardiac function, or
             electrocardiographic evidence of acute ischemic or active conduction system
             abnormalities

          -  Prior anthracycline, platinum salt, or taxane for any malignancy

          -  Known or active hepatitis B or C with abnormal liver function tests

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Intrinsic lung disease resulting in moderate to severe dyspnea

          -  History of a major organ allograft or condition requiring chronic immunosuppression,
             e.g., kidney, liver, lung, heart, bone marrow transplant, or autoimmune diseases; this
             includes treatment with corticosteroids within one month (dose of >= 10 mg/day
             methylprednisolone equivalent) (excluding inhaled steroids); patients who have
             received corneal transplants, cadaver skin, or bone transplants are eligible

          -  Nervous system disorder (paresthesias, peripheral motor neuropathy, or peripheral
             sensory neuropathy) >= grade 2, per the Common Terminology Criteria for Adverse Events
             version 4.0 (CTCAE v4.0)

          -  Conditions that would prohibit administration of corticosteroids