Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This neoadjuvant chemotherapy protocol focusing on triple-negative breast cancers alone will gather a foundation of primary tumor and axillary lymph nodal response to primary chemotherapy and ongoing correlated disease-free (DFS) and overall survival (OS) outcome data. This comparative data can then be used in building subsequent trials.

Detailed Description
-----------------
Women with a diagnosed triple-negative proxy of basal-like breast cancer confirmed on a core biopsy and larger than 2 cm will be treated neoadjuvantly with the Livingston metronomic regimen of 12 weeks of weekly doxorubicin 24 mg/m2 and daily oral cyclophosphamide 60 mg/m2 followed by 12 successive weeks of taxol 80 mg/m2 and carboplatin AUC 2. Although clinical response will be evaluated prior to surgery, the primary end-point is the pathologic response. Secondary end-points will be DFS and OS based upon standard of care surveillance. A pathologic complete response (pCR) will require no histologic evidence of residual malignant cells seen in the primary tumor area specimen or the lymph nodes. Standard of care surgery and radiation therapy will be undertaken.

Official Title
-----------------
Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Doxorubicin / Cyclophosphamide / Paclitaxel / Carboplatin
* Procedure: Definitive Surgery
* Radiation: Radiotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with Estrogen Receptor (ER), Progesterone Receptor (PR),and HER2 negative invasive breast cancer confirmed on core biopsy.(Note: HER2 negative by FISH preferred; HER2 0 or 1+ by IHC acceptable) Primary tumor size 2cm or greater by physical exam or radiographic measurements.(Note: Locally advanced T4 or inflammatory breast cancer is eligible.) Assessment of pre-treatment axillary lymph nodal status (Note: FNA biopsy if palpable or sentinel lymph node biopsy (SLNB) if not palpable preferred; clinical exam acceptable.) Absolute neutrophil count > 1500 mm3 and platelet count > 100,000 mm3 Normal myocardial left ventricular function Serum creatinine < 2.0 mg/dl Total bilirubin and AST < 3X upper limits normal Exclusion Criteria: Recurrent or metastatic breast cancer findings (Note: If oncologically felt to be a second breast primary, patient eligible for this protocol) Another active cancer present Medical contraindications to chemotherapy or surgery First trimester pregnancy Breast feeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant metronomic AC followed by weekly TC<br>Neoadjuvant chemotherapy with metronomic AC followed by weekly TC then surgery | Drug: Doxorubicin / Cyclophosphamide / Paclitaxel / Carboplatin<br>* DOXORUBICIN 24mg/m2 IV plus CYCLOPHOSPHAMIDE 60mg/m2 PO weekly x 12 successive weeks followed by PACLITAXEL 80mg/m2 IV over 1 hour plus CARBOPLATIN AUC 2 IV weekly x 12 successive weeks<br>* Other names: Metronomic;Procedure: Definitive Surgery<br>* Standard of care definitive surgery as determined by medical provider<br>Radiation: Radiotherapy<br>* Standard of care RADIATION THERAPY as indicated<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) Pathologic Response | Pathologic measurement post-surgery viable primary tumor mass | Upon completion therapy after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Triple negative (ER/PR negative; HER2 negative)