Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer. PURPOSE: This randomized phase II trial is comparing two different regimens of combination chemotherapy given together with or without trastuzumab to see how well they work in treating patients with stage II or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare 2 neoadjuvant chemotherapy regimens (docetaxel, doxorubicin hydrochloride, and cyclophosphamide [TAC] vs doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin [ACAC]), in terms of toxicities and effectiveness as defined by the pathological complete remission rate, in patients with non HER2/neu overexpressing stage II or III breast cancer. Evaluate the probability of achieving a pathological complete remission when adding trastuzumab (Herceptin®) to ACAC in the subset of patients with HER2/neu overexpressing stage II or III breast cancer. Secondary Identify prognostic and predictive markers of outcome, recurrence, and targets of therapy. OUTLINE: This is a randomized study. Patients with non HER2/neu overexpressing tumors are randomized to 1 of 2 treatment arms. Patients with HER2/neu overexpressing tumors are assigned to arm III. Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses. Arm II: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses. Arm III: Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin. Within 4 weeks after completion of chemotherapy with or without trastuzumab (Herceptin®), all patients undergo surgery. PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Official Title
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Randomized Phase II Study of Docetaxel, Adriamycin, and Cytoxan (TAC) Versus Adriamycin/Cytoxan, Followed by Abraxane/Carboplatin (ACAC) +/- Trastuzumab as Neoadjuvant Therapy for Patients With Stage II-III Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride
* Biological: Trastuzumab
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven infiltrating ductal or lobular breast carcinoma Stage II or III disease Inflammatory breast cancer allowed Hormone-receptor status not specified PATIENT CHARACTERISTICS: ECOG performance status < 2 Male or female Menopausal status not specified (for female patients) Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin normal (except for patient's with Gilbert's disease) Creatinine ≤ 1.2 mg/dL Creatinine clearance ≥ 70 mL/min Ejection fraction ≥ 50% on MUGA No neuropathy ≥ grade 1 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective nonhormonal contraception No prior malignant disease within the past 5 years, excluding: Squamous cell or basal cell skin carcinoma Stage I or in situ cervical carcinoma No noninvasive (in situ) breast carcinoma within the past 5 years PRIOR CONCURRENT THERAPY: At least 5 years since prior antiestrogen treatment for any indication other than breast cancer prevention (tamoxifen, raloxifene, or an aromatase inhibitor) No prior radiotherapy to the chest wall

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide<br>Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses. | Drug: cyclophosphamide<br>* Given IV<br>Drug: docetaxel<br>* Given IV<br>Drug: doxorubicin hydrochloride<br>* Given IV<br>|
| Experimental: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin<br>Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses. | Drug: cyclophosphamide<br>* Given IV<br>Drug: doxorubicin hydrochloride<br>* Given IV<br>Drug: Carboplatin<br>* Given IV<br>Drug: Paclitaxel<br>* Given IV<br>|
| Experimental: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and trastuzumab<br>Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin. | Drug: cyclophosphamide<br>* Given IV<br>Drug: doxorubicin hydrochloride<br>* Given IV<br>Biological: Trastuzumab<br>* Given IV<br>Drug: Carboplatin<br>* Given IV<br>Drug: Paclitaxel<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Count of Patients With Pathologic Complete Response (pCR) | pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in primary tumor and lymph nodes. | At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months | 
| Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1. | RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy. The higher the RCB score, the more residual breast cancer there is in the breast and lymph nodes: RCB-0 = No residual breast cancer RCB-I = Small amount of residual breast cancer RCB-II = Moderate amount of residual breast cancer RCB-III = Extensive (a lot of) residual breast cancer | At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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inflammatory breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, male breast cancer, Paget disease of the breast with invasive ductal carcinoma, invasive ductal breast carcinoma with predominant intraductal component, invasive ductal breast carcinoma, medullary ductal breast carcinoma with lymphocytic infiltrate, comedo ductal breast carcinoma, invasive lobular breast carcinoma with predominant in situ component, invasive lobular breast carcinoma, mucinous ductal breast carcinoma, papillary ductal breast carcinoma, tubular ductal breast carcinoma