Docetaxel and Carboplatin With or Without Trastuzumab Before Surgery in Treating Women With Locally Advanced Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether docetaxel and carboplatin are more effective with or without trastuzumab in treating breast cancer. PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with carboplatin and trastuzumab before surgery works compared to docetaxel and carboplatin alone before surgery in treating women with locally advanced breast cancer.

Official Title
-----------------
Neoadjuvant Treatment and Molecular Characterization of Locally Advanced Breast Cancer

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

Intervention / Treatment
-----------------
* Biological: trastuzumab
* Drug: carboplatin
* Drug: docetaxel
* Biological: trastuzumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed infiltrating adenocarcinoma of the breast Primary breast cancer > 5cm, or skin/chest wall involvement, any N, without evidence of metastasis. No prior radiation to the involved breast ECOG (Electrocochleography) performance status 0-2 Age 18 years to 80 years Absolute Neutrophil count > 1500 cell/μl, platelet count > 100000 cells/μl and hemoglobin > 9 g/dl All liver function tests < upper limit of normal Serum creatinine < 2.0 mg/dl Normal left ventricular ejection fraction (LVEF) as determined by MUGA (Multiple Gated Acquisition) scan or echocardiogram HER-2/neu status is determined by a FISH (Fluorescence in situ hybridization) test. [FISH (+) is HER-2/neu (+)] If female of childbearing potential, pregnancy test is negative If premenopausal and not surgically sterilized, the patient agrees to use effective birth control method for the duration of the study Informed consent has been obtained Exclusion Criteria: Non-confirmed infiltrating adenocarcinoma breast cancer Evidence of metastasis Previous chemotherapy using the drugs proposed in this study, specifically Herceptin®, Taxotere®, and/or Carboplatin Prior radiation to the involved breast Recent breast cancer drug therapy within last 5 years of any form History of allergy to polysorbate or castor oil Ongoing active infection Concurrent life-limiting disease with a life expectancy of less than one year Past or current history of other malignancy within the past 5 years which could affect the diagnosis or assessment of breast cancer, except for curatively treated non-melanoma skin cancer and/or in situ carcinoma of the cervix Pregnancy, nursing, fertile women who do not use birth control device Inability to give informed consent Patients with pre-existing peripheral neuropathy > grade 2

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (neoadjuvant therapy)<br>see intervention description | Drug: carboplatin<br>* Cycle 1-8 Day 1 or 2 AUC = 6 IV<br>Drug: docetaxel<br>* Cycle 1-8 Day 1 or 2: 75 mg/m2 IV<br>* Other names: Taxotere;Biological: trastuzumab<br>* Cycle 1-4 pre-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 5-7 post-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV<br>* Other names: Herceptin;|
| Experimental: Arm II (neoadjuvant therapy)<br>please see intervention description | Biological: trastuzumab<br>* Cycle 5-7 post-op only Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV<br>* Other names: Herceptin;Drug: carboplatin<br>* Cycle 1-8 Day 1 or 2 AUC = 6 IV<br>Drug: docetaxel<br>* Cycle 1-8 Day 1 or 2: 75 mg/m2 IV<br>* Other names: Taxotere;|
| Experimental: HER2/neu negative patients<br>please see intervention description | Drug: carboplatin<br>* Cycle 1-8 Day 1 or 2 AUC = 6 IV<br>Drug: docetaxel<br>* Cycle 1-8 Day 1 or 2: 75 mg/m2 IV<br>* Other names: Taxotere;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively. | Objective response rate of patients treated with Taxotere/carboplatin with or without Herceptin preoperatively. Objective response equals the combination of complete response (CR), partial response (PR) and marginal response (MR). Tumor size was assessed by (1) physical examination, (2) mammography and (3) MRI. 5 response groups: complete response (CR), partial response (PR), marginal response (MR), stable disease (SD) & disease progression (DP). Pathologic response assigned into 2 groups: pCR and non-pCR. pCR-no evidence of residual invasive disease in specimen. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Tumor Response by Physical Exam and Imaging Studies |  | 5 years | 
| Tumor Response Assessment | Measured by physical examination compared to breast mammography and MRI assessment | 5 years | 
| Clinico-histologic Predictors of pCR (Pathologic Complete Response) |  | 5 years | 
| Pathologic Nodal Status | According to Primary Tumor Response Pathologic lymph node status N0 Axillary and other nearby lymph nodes do not have cancer (when looked at under a microscope) N1 Micrometastases (very small clusters of cancer) OR 1-3 axillary lymph nodes have cancer AND/OR Internal mammary nodes have tiny amounts of cancer found on sentinel node biopsy N2 4-9 axillary lymph nodes have cancer OR Internal mammary nodes have cancer, but axillary lymph nodes do not have cancer N3 10 or more axillary lymph nodes have cancer OR Infraclavicular (under the clavicle) nodes have cancer OR Internal mammary nodes have cancer plus 1 or more axillary lymph nodes have cancer OR 4 or more axillary lymph nodes have cancer plus internal mammary nodes have cancer or micrometastases found on sentinel node biopsy OR Supraclavicular (above the clavicle) nodes have cancer | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage II breast cancer