Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer

Inclusion Criteria

• Female patients, age ≥18 years
• Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
• Triple-negative tumors are defined as:
• For HER2-negative:
• Fluorescence in situ hybridization (FISH)-negative (defined by ratio 1500/μL
• Platelets ≥100,000/μL
• Hemoglobin ≥10 g/dL
• Adequate hepatic and renal function with:
• Serum bilirubin ≤ the institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x institutional ULN
• Alkaline phosphatase ≤2.5 x institutional ULN
• Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥40 mL/min
• Left ventricular ejection fraction (LVEF) ≥50% by multigated acquisition (MUGA) or echocardiogram (ECHO)
• Bilateral, synchronous breast cancer is allowed if one primary tumor meets the inclusion criteria
• Knowledge of the investigational nature of the study and ability to provide consent for study participation
• Ability and willingness to comply with study visits, treatment, testing, and other study procedures

Exclusion Criteria

• Previous treatment for this breast cancer
• Previous treatment with paclitaxel or carboplatin
• Previous treatment with sunitinib or other angiogenic inhibitors (including, but not limited to bevacizumab, sorafenib, thalidomide)
• Any of the following within the 12 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident including transient ischemic attack, or pulmonary embolus
• Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy)
• Ongoing cardiac dysrhythmias grade ≥2, atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec
• Major surgery, significant traumatic injury, or radiation therapy within 4 weeks of starting study treatment. An interval of at least 1week is required following minor surgical procedures, with the exception of placement of a vascular access device
• Grade 3 hemorrhage within 4 weeks of starting study treatment
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• Known human immunodeficiency virus (HIV) infection or other serious infection
• Concomitant treatment with drugs having proarrhythmic potential including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide
• Concurrent use of the potent CYP3A4 inhibitors ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole and CYP3A4 inducers rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. Grapefruit and grapefruit juice is prohibited. Alternative therapies should be used when available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be approved by the Study Chair
• Known or suspected hypersensitivity to drugs containing Cremophor®EL (polyoxyethylated castor oil) such as cyclosporine or teniposide
• Pregnancy or breast-feeding. Negative serum pregnancy test is required within 7 days prior to first study treatment (Day 1, Cycle ) for all women of childbearing potential. Patients of childbearing potential must agree to use a birth control method that is approved by their study physician while receiving study treatment and for three months after the last dose of study treatment. Patients must agree to not breast-feed while receiving study treatment
• Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator (SERM). Patients must hav