S0012 Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Filgrastim in Treating Women With Inflammatory or Locally Advanced Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether combination chemotherapy is more effective with or without filgrastim in treating breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combining doxorubicin, cyclophosphamide, and paclitaxel with or without filgrastim in treating women who have inflammatory or locally advanced breast cancer.

Detailed Description
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OBJECTIVES: Compare the microscopic pathologic response rates in women with inflammatory or locally advanced breast cancer treated with standard neoadjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel vs weekly doxorubicin and daily oral cyclophosphamide with filgrastim (G-CSF) followed by weekly paclitaxel. Compare the toxic effects of these regimens in this patient population. Compare the delivered dose intensity of these regimens in this patient population. Evaluate the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease status (inflammatory vs other). Patients are randomized to one of two treatment arms. Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV on day 1. Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Three weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour weekly on day 1 for a total of 12 weeks. Arm II: Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and filgrastim (G-CSF) subcutaneously on days 2-7. Treatment repeats weekly for a total of 15 courses of doxorubicin and cyclophosphamide and 16 courses of G-CSF in the absence of disease progression or unacceptable toxicity. One week after completion of G-CSF, patients receive paclitaxel as in arm I. Within 3-6 weeks after completion of chemotherapy, patients with stable or responsive disease undergo surgical resection of tumor and affected nodes. After surgery, patients may receive radiotherapy or additional chemotherapy and/or hormonal therapy at the discretion of the treating physician. Patients are followed every 6 months for 1 year and then annually for 4 years. PROJECTED ACCRUAL: A total of 350 patients (175 per treatment arm) will be accrued for this study within 3 years.

Official Title
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A Comparative Randomized Study of Standard Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel Vs. Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel As Neoadjuvant Therapy For Inflammatory and Locally Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: filgrastim
* Drug: cyclophosphamide
* Drug: doxorubicin
* Drug: paclitaxel
* Procedure: surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed inflammatory or locally advanced breast cancer Stage IIB (T3, N0, M0), IIIA (T3, N1-2, M0 or T0-2, N2, M0), or IIIB (T4, any N, M0 or any T, N3, M0) Unresectable or otherwise appropriate for neoadjuvant therapy Confirmed by core needle or incisional biopsy Punch biopsy allowed if invasive disease is documented No distant metastases Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: Not specified Sex: Female Menopausal status: Not specified Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than upper limit of normal (ULN) SGOT or SGPT no greater than 2 times ULN Renal: Creatinine no greater than ULN Cardiovascular: No congestive heart failure or angina pectoris LVEF greater than lower limit of normal Other: No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for breast cancer Endocrine therapy: No prior hormonal therapy for breast cancer Radiotherapy: No prior radiotherapy for breast cancer Surgery: No prior definitive surgery for breast cancer Other: No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: AC followed by P<br>doxorubicin and cyclophosphamide followed by paclitaxel followed by surgery | Drug: cyclophosphamide<br> <br> * Other names: cytoxan;Drug: doxorubicin<br> <br> * Other names: Adriamycin;Drug: paclitaxel<br> <br> Procedure: surgery<br> <br> |
| Experimental: AC+G followed by P<br>weekly doxorubicin and daily cyclophosphamide with filgrastim followed by paclitaxel followed by surgery | Biological: filgrastim<br> <br> * Other names: G-CSF;Drug: cyclophosphamide<br> <br> * Other names: cytoxan;Drug: doxorubicin<br> <br> * Other names: Adriamycin;Drug: paclitaxel<br> <br> Procedure: surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of microscopic pathologic response rates |  | no sooner than 21 days after chemo | 
| Toxicity |  | during chemo and at surgery | 
| Comparison of delivered dose intensity |  | after chemo | 
| Correlation of microscopic pathologic complete response with clinical complete response at the primary tumor site |  | no sooner than 21 days after chemo | 

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