NECTAR Everolimus Plus Cisplatin in Triple (-) Breast Cancer

Inclusion Criteria

• Female patients ≥18 years of age.
• Clinical/pathological documentation of residual disease after neo-adjuvant therapy.
• Patients with synchronous bilateral cancers are eligible only if:
• Index cancer is triple-negative, defined as ER-, PR-, and HER2-.
• HER2 negative tumors. HER2 negativity must be confirmed by one of the following:
• FISH-negative (FISH ratio 1000/mm3
• Platelet count ≥100,000/mm3
• Hemoglobin >9 g/dL
• Adequate liver function, defined by:
• AST and ALT ≤2.5 x the upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN (unless the patient has grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin).
• Adequate renal function, defined by:
• Serum creatinine ≤1.5 x ULN
• Complete staging work-up ≤24 weeks prior to initiation of study treatment with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and either a positron emission tomography (PET) scan or a bone scan.
• Adequate cardiac function, defined by a left ventricular ejection fraction (LVEF) value of >50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO).
• Patients with previous history of invasive cancers (including breast cancer) are eligible if definitive treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease.
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• Patient must be accessible for treatment and follow-up.
• Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter.
• Able to swallow and retain oral medication.
• Patient must be willing to undergo breast biopsies as required by the study protocol.
• All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.

Exclusion Criteria

• Women who are pregnant or breastfeeding.
• History of previously treated ductal carcinoma in situ (DCIS) is acceptable.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus);
• Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years.
• Patients who have any severe and/or uncontrolled medical conditions such as:
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• Symptomatic congestive heart failure of New York heart Association Class III or IV
• active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA),
• known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air),
• active, bleeding diathesis;
• Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Concurrent severe, uncontrolled infection or intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
• Mental condition that would preven