| Is your age greater than or equal to 18 yrs? |
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| Are you female? |
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| Do you have HER2 Negative Breast Cancer? |
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| Do you have any of these conditions: Do you have HER2 Negative Breast Cancer?? |
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| SCREENING PRIOR TO INITIATING CHEMOTHERAPY |
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| Patient must have an Eastern Cooperative Oncology Group (ECOG) performance |
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| status of 0 or 1 The diagnosis of invasive adenocarcinoma of the breast must |
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| have been made by core needle biopsy |
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| The primary breast tumor must be palpable and measure greater than or equal |
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| 0 cm on physical exam |
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| The regional lymph nodes can be cN0, cN1, or cN2a |
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| Histological grade II or III tumor |
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| Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram |
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| ultrasound, and/or MRI) within 6 weeks prior to initiating chemotherapy. If |
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| suspicious or abnormal, FNA or core biopsy is recommended, also within 6 weeks |
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| prior to initiating chemotherapy. Findings of these evaluations will be used |
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| to determine the nodal status prior to initiating chemotherapy |
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| Nodal status - negative: Imaging of the axilla is negative; Imaging is suspicious or abnormal but the FNA or core biopsy of the questionable node(s) on imaging is negative |
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| Nodal status - positive: FNA or core biopsy of the node(s) is cytologically or histologically suspicious or positive. Imaging is suspicious or abnormal but FNA or core biopsy was not performed |
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| Tumor specimen obtained at the time of diagnosis must have ER and progesterone |
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| receptor (PgR) analysis assessed by current ASCO/CAP Guidelines. Patients are |
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| eligible with either hormone receptor-positive or hormone receptor-negative |
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| tumors |
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| Tumor specimen obtained at the time of diagnosis must have been determined to |
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| be HER2-negative as follows |
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| Immunohistochemistry (IHC) 0-1+; or |
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| IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to chromosome enumeration probe 17 (CEP17) less than 2.0, and if reported, average HER2 gene copy number less than 4 signals/cells; or |
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| ISH non-amplified with a ratio of HER2 to CEP17 less than 2.0, and if reported, average HER2 gene copy number less than 4 signals/cells |
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| Blood counts performed within 6 weeks prior to initiating chemotherapy must |
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| meet the following criteria |
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| absolute neutrophil count (ANC) must be greater than or equal 1200/mm3 |
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| platelet count must be greater than or equal 100,000/mm3; and |
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| hemoglobin must be greater than or equal 10 g/dL |
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| The following criteria for evidence of adequate hepatic function performed |
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| within 6 weeks prior to initiating chemotherapy must be met |
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| total bilirubin must be less than or equal to upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and |
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| alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and |
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| aspartate aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab |
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| Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the alkaline phosphatase is greater than the ULN but less than or equal to 2.5 x ULN, the AST must be less than or equal to the ULN. If the AST is greater than the ULN but less than or equal to 1.5 x ULN, the alkaline phosphatase must be less than or equal to ULN. Note: If alanine aminotransferase (ALT) is performed instead of AST (per institution's standard practice), the ALT value must be less than or equal to 1.5 x ULN; if both were performed, the AST must be less than or equal to 1.5 x ULN |
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| Patients with AST or alkaline phosphatase greater than ULN are eligible for |
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| inclusion in the study if liver imaging (CT, MRI, PET-CT, or PET scan) |
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| performed within 6 weeks prior to initiating chemotherapy does not demonstrate |
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| metastatic disease and the requirements in next criteria are met |
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| Patients with alkaline phosphatase that is greater than ULN but less than or |
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| equal to 2.5 x ULN or unexplained bone pain are eligible for inclusion in the |
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| study if a bone scan, PET-CT scan, or positron emission tomography (PET) scan |
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| performed within 6 weeks prior to initiating chemotherapy does not demonstrate |
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| metastatic disease |
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| Serum creatinine performed within 6 weeks prior to initiating chemotherapy |
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| must be less than or equal to 1.5 x ULN for the lab |
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| The left ventricular ejection fraction (LVEF) assessment by echocardiogram or |
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| multi-gated acquisition (MUGA) scan performed within 90 days prior to |
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| initiating chemotherapy must be greater than or equal 55 percent regardless of |
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| the facility's lower limit of normal (LLN) |
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| Patients with reproductive potential must agree to use an effective non- |
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| hormonal method of contraception during therapy and for at least 7 months |
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| after the last dose of study |
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| MAIN STUDY ENROLLMENT |
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| Tumor determined to have abnormal HER2-driven signaling activity based on the |
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| CELx HSF test |
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| T4 tumors including inflammatory breast cancer |
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| FNA alone to diagnose the breast cancer |
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| Excisional biopsy or lumpectomy performed prior to initiating chemotherapy |
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| Surgical axillary staging procedure prior to initiating chemotherapy. Pre- |
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| neoadjuvant therapy sentinel node biopsy is not permitted. (FNA or core biopsy |
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| is acceptable.) |
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| Definitive clinical or radiologic evidence of metastatic disease. Required |
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| imaging studies must have been performed within 6 weeks prior to initiating |
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| chemotherapy |
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| Synchronous bilateral invasive breast cancer. (Patients with synchronous |
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| and/or previous contralateral ductal carcinoma in situ [DCIS] or lobular |
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| carcinoma in situ [LCIS] are eligible.) |
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| Any previous history of ipsilateral invasive breast cancer or ipsilateral |
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| DCIS. (Patients with synchronous or previous ipsilateral LCIS are eligible.) |
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| Previous therapy with anthracycline, taxanes, trastuzumab, or other HER2 |
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| targeted therapies for any malignancy |
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| Any sex hormonal therapy, e.g., birth control pills, ovarian hormone |
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| replacement therapy, etc. (These patients are eligible if this therapy is |
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| discontinued prior to initiating chemotherapy.) |
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| History of non-breast malignancies (except for in situ cancers treated only by |
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| local excision and basal cell and squamous cell carcinomas of the skin) within |
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| years prior to initiating chemotherapy |
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| Cardiac disease (history of and/or active disease) that would preclude the use |
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| of the drugs included in the treatment regimens. This includes but is not |
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| confined to |
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| Active cardiac disease: angina pectoris that requires the use of anti-anginal medication; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic pericarditis |
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| History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function; history of documented congestive heart failure (CHF); and documented cardiomyopathy |
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| Uncontrolled hypertension defined as sustained systolic BP greater than 150 |
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| mmHg or diastolic BP greater than 90 mmHg. (Patients with initial BP |
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| elevations are eligible prior to initiating chemotherapy if initiation or |
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| adjustment of BP medication lowers pressure.) |
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| Active hepatitis B or hepatitis C with abnormal liver function tests |
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| Intrinsic lung disease resulting in dyspnea |
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| Poorly controlled diabetes mellitus |
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| Active infection or chronic infection requiring chronic suppressive |
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| antibiotics |
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| Patients known to be HIV positive |
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| Nervous system disorder (paresthesia, peripheral motor neuropathy, or |
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| peripheral sensory neuropathy) greater than or equal to grade 2, per the CTCAE |
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| v4.0 |
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| Malabsorption syndrome, ulcerative colitis, resection of the stomach or small |
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| bowel, or other disease significantly affecting gastrointestinal function |
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| Other non-malignant systemic disease that would preclude treatment with any of |
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| the treatment regimens or would prevent required follow-up |
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| Conditions that would prohibit administration of corticosteroids |
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| Chronic daily treatment with corticosteroids with a dose of greater than or |
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| equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids) |
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| Known hypersensitivity to any of the study drugs or any of the ingredients or |
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| excipients of these drugs (e.g., Cremophor EL), including sensitivity to |
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| benzyl alcohol |
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| Pregnancy or lactation at the initiation of chemotherapy. (Note: Pregnancy |
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| testing must be performed within 2 weeks prior to initiating chemotherapy |
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| according to institutional standards for women of childbearing potential.) |
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| Psychiatric or addictive disorders or other conditions that, in the opinion of |
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| the investigator, would preclude the patient from meeting the study |
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| requirements |
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