Combination Chemotherapy With or Without Darbepoetin Alfa in Treating Women With 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. Colony-stimulating factors, such as darbepoetin alfa, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy together with darbepoetin alfa after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy and darbepoetin alfa are more effective than combination chemotherapy alone in treating stage III breast cancer. PURPOSE: This randomized clinical trial is studying how well giving combination chemotherapy together with darbepoetin alfa works compared to combination chemotherapy alone in treating women with stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary Compare the disease-free survival rate in women with stage III breast cancer treated with adjuvant chemotherapy with vs without darbepoetin alfa. Secondary Compare local recurrence and overall survival in patients receiving these regimens. Compare toxicity of these regimens in these patients. Compare quality of life and fatigue frequency in patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according the chemotherapy regimen (CEF vs TAC). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive 1 of the following regimens: Regimen CEF: Patients receive cyclophosphamide IV, epirubicin hydrochloride IV, and fluorouracil IV on day 1. Regimen TAC: Patients receive docetaxel IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression and unacceptable toxicity. Arm II: Patients receive 1 of the following regimens: Regimen CEF: Patients receive regimen CEF as in arm I. Patients receive darbepoetin alfa if hemoglobin falls to ≤ 13.0 g/dL. Darbepoetin alfa is discontinued when hemoglobin rises to > 14.0 g/dL. Regimen TAC: Patients receive TAC as in arm I and darbepoetin alfa as in arm II, regimen CEF. Quality of life is assessed at baseline, before each chemotherapy course, at the completion of study therapy, and at 6 and 12 months. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 1,234 patients will be accrued for this study.

Official Title
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Adjuvant Therapy of Breast Cancer: Impact of Erythropoiesis Stimulating Factors on Event Free Survival High Risk Breast Cancer Treatment

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: darbepoetin alfa
* Drug: cyclophosphamide
* Drug: docetaxel
* Drug: doxorubicin hydrochloride
* Drug: epirubicin hydrochloride
* Drug: fluorouracil


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed breast cancer Stage III disease (pT1, N2-3, M0) No metastatic disease by thoracic x-ray, full-body bone scan, and liver sonography No inflammatory disease or Paget's disease Disease completely resected (R0) and ≥ 10 axillary lymph nodes removed Underwent surgery approximately 42 days ago At least 9 positive lymph nodes No prior sequential mastectomy Hormone receptor status not specified PATIENT CHARACTERISTICS: Female Menopausal status not specified ECOG performance status 0-1 WBC ≥ 3,500/mm^3 Creatinine ≤ 1.4 mg/dL Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 2.0 mg/dL No pre-existing symptomatic peripheral neuropathy Not pregnant or nursing No hypersensitivity to darbepoetin alfa, epoetin alfa, or any of their components No other malignancy except curatively treated basal cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: See Disease Characteristics No participation in another clinical study No prior therapies that would preclude study participation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: darbepoetin alfa|nan|
|Drug: cyclophosphamide|nan|
|Drug: docetaxel|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: epirubicin hydrochloride|nan|
|Drug: fluorouracil|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival at 6 months to 5 years after treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival at 6 months to 5 years after treatment |  |  | 
| Toxicity by NCI toxicity criteria at every course and periodically thereafter |  |  | 
| Anemia and cognitive function by Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) at every course |  |  | 
| Local relapses at 6 months to 5 years after treatment |  |  | 

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