Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
Neoadjuvant Carbo/Paclitaxel Followed by Doxorubicin/Cyclophosphamide in Breast Cancer
This is a phase II single-arm, open-label, prospective study to evaluate the efficacy of the
 low dose weekly Carboplatin/Paclitaxel followed by dose-dense Doxorubicin/Cyclophosphamide in
 subjects with triple-negative breast cancer in neoadjuvant settings.
Inclusion Criteria:

 1. Subjects must have histologically or cytologically confirmed invasive breast cancer
 which meets the following criteria:

 1. Estrogen Receptor (ER) and Progesterone Receptor (PR)-negative as defined by
 local standard clinical immunohistochemistry (IHC) < 1%.

 2. HER2-negative using local standard testing. Negative is defined as IHC 0 or 1+
 (if 2+, must reflex to ISH method). If ISH method is used, ratio < 2 is
 considered negative.

 3. Clinical tumor size of at least 2.1 cm (T2) by palpation or imaging, regardless
 of the ipsilateral regional lymph node status, or any tumor size but with
 ipsilateral regional lymph nodes involved by the tumor (any T if ipsilateral
 regional node positive). Subjects with inflammatory breast cancer are eligible.
 If bilateral breast cancer is present, the subject is eligible if the
 contralateral tumor is DCIS only (without any invasive disease on biopsy) or
 another invasive breast cancer of any size that is also ER, PR and HER2 negative.

 4. Any radiographic abnormal ipsilateral regional lymph nodes or any clinically
 concerning ipsilateral regional lymph nodes with the exception of internal
 mammary nodes should be sampled with percutaneous biopsy, but no sentinel
 axillary lymph node mapping/biopsy is allowed before chemotherapy. If clinically
 node negative (cNO), pre-chemotherapy ipsilateral sentinel axillary lymph node
 mapping/biopsy is not allowed.

 2. Candidate for neoadjuvant chemotherapy.

 3. Age > 18 years and < 75 years

 4. ECOG Performance Status < 1.

 5. Left ventricular ejection fraction (LVEF) ≥ LLN (per institutional normal) determined
 by

 6. Adequate organ and marrow function as determined by study protocol

 7. Non Pregnant. Women of childbearing potential must have a negative pregnancy test (HCG
 serum or urine) within 30 days prior to study registration and to be repeated if not
 done within 7 days of starting chemotherapy.

 1. Female subjects must meet one of the following:

 -  Natural postmenopausal before the screening visit defined as no menses at
 any time in the preceding 12 consecutive months, or

 -  Prior bilateral oophorectomy or bilateral tubal ligation, or

 -  If they are of childbearing potential, agree to practice two effective
 methods of contraception per discussion with the treating physicians from

 2. Male subjects, even if surgically sterilized (i.e., status post vasectomy) must
 agree to one of the following:

 -  Practice effective barrier contraception during the entire study treatment
 period and through 90 days after the last study drug dose, or

 -  Agree to practice true abstinence when this is in line with the preferred
 and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar,
 ovulation, symptothermal, postovulation methods] and withdrawal are not
 acceptable methods of contraception.)

 8. Ability to understand a written informed consent document, and the willingness to sign
 it.

 Exclusion Criteria:

 1. Prior chemotherapy or radiation therapy for invasive breast cancer within 6 months
 before registration.

 2. Prior investigational drugs or interventions for invasive breast cancer within 6
 months before registration are not allowed. Prior participation in
 window-of-opportunity trials without therapeutic intent is allowed if intervention is
 no more than 3 weeks duration.

 3. Stage IV metastatic breast cancer

 4. History of allergic reactions attributed to compounds of similar chemical composition
 to chemotherapy to be used in this study.

 5. Breastfeeding women. Cytotoxic chemotherapy is drug with the potential for teratogenic
 or abortifacient effects. Due to unknown but potential risk for adverse events in
 nursing infants secondary to treatment of the mother with cytotoxic chemotherapy,
 breastfeeding should be discontinued.

 6. Baseline peripheral neuropathy of severity > grade 1

 7. Other invasive cancer diagnosis within the past 5 years other than non-melanoma skin
 cancer.

 8. Prior axillary lymph node dissection that preclude patient from surgical evaluation of
 axillary lymph node status.