Preoperative Epirubicin Paclitaxel Aranesp Study (PREPARE)

Study Overview
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Brief Summary
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The present clinical trial will investigate the efficacy of a sequential interval-shortened and dose-intensified preoperative use of epirubicin, paclitaxel and CMF with preoperative sequential administration of epirubicin and cyclophosphamide followed by paclitaxel in breast cancer. In addition, the influence of darbepoetin alfa on the response rate and quality of life is to be investigated in both treatment arms.

Detailed Description
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Arm A: Sequential treatment in standard doses with Epirubicin (90 mg/m2)/cyclophosphamide (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4×. Pegfilgratim should be used as secondary preventive after febrile neutropenia in the standard arm of the study, or in exceptional cases also after severe febrile neutropenia necessitating postponement of the treatment by more than one week ± Darbepoetin alfa 1 × 4.5 µg/kg of body weight every two weeks with the start of the first epirubicin dose (day 1) until 14 days after the last dose of paclitaxel Daily oral intake of 200 mg iron unless there complications occur with taking iron Arm B: sequential dose-intensified, interval-shortened treatment with Epirubicin (150 mg/m2) d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF (600/40/600 mg/m2) d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg after epirubicin and/or paclitaxel: subcutaneous injection on day 2. After CMF pegfilgrastim should be used as a secondary preventive measure ± Darbepoetin alfa 1 × 4.5 µg/kg of body weight every two weeks with the start of the first dose of epirubicin (day 1) until 14 days after the last dose of CMF Daily oral dose of 200 mg iron unless complications occur in taking iron. Primary goal: Determining the relapse-free survival time and overall survival after dose-intensified sequential preoperative chemotherapy including anthracycline and taxan and/or after preoperative chemotherapy including anthracycline followed by taxan in a standard dose

Official Title
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Randomized Comparison of a Preoperative, Dose-Intensified, Interval-Shortened, Sequential Chemotherapy With Epirubicin, Paclitaxel and CMF ± Darbepoetin Alfa Versus a Preoperative, Sequential Chemotherapy With Epirubicin and Cyclophosphamide Followed by Paclitaxel in Standard Dosage ± Darbepoetin Alfa in Patients With Primary Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin, paclitaxel, cyclophosphamide, Methotrexate, 5 FU, darbepoetin alfa
* Drug: Epirubicin, Cyclophosphamide, Paclitaxel, dabepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed breast cancer: at least three fast biopsies. Primary tumor ≥2 cm acc. to clinical measurement or manifestation of an inflammatory breast cancer. No systemic metastasis, exclusion by chest x-ray, sonogram of the upper abdomen and skeletal scintiscan. Age ≥18 years and ≤65 years. ECOG < 2/WHO 0-1 Adequate organ function defined as SGOT and bilirubin ≤ 1.5× upper limit WBC ≥ 3000 /µL Neutrophils ≥ 1000 /µL Platelets ≥ 100,000 /µL Serum creatinine < 2.0 mg/dL Unremarkable heart echo No florid hepatitis Written consent to participate in the treatment optimization protocol Exclusion Criteria: Multicentricity in various quadrants (contact the study office) Known allergy to E. coli-produced medication Known allergy to medication containing cremophor (e.g., cyclosporin A) Patients receiving immunosuppressant therapy Lack of consent after informing the patient Lack of willingness to keep and disclose personal medical data as part of the study Pregnancy, nursing Secondary malignancy, excluding basalioma of the skin or carcinoma in situ of the cervix that has received curative therapy Pre-existing treatment-resistant cardiac disease, coronary heart disease, arrhythmias, cardiac insufficiency Patients with uncontrolled hypertension (diastolic >95 mmHg) A history of convulsions Known hypersensitivity to darbepoetin alfa or any of its other ingredients or a known hypersensitivity to r-HuEPO

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: epirubicin, paclitaxel and CMF +/- darbepoetin<br>Epirubicin (90 mg/m2) d1, q21d - 4× / cyclophosphamide (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4× +/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first epirubicin dose (day 1) to 14 days after the last dose of paclitaxel | Drug: Epirubicin, paclitaxel, cyclophosphamide, Methotrexate, 5 FU, darbepoetin alfa<br>* Epirubicin (90 mg/m2) d1, q21d - 4× / cyclophosphamide (600 mg/m2) d1, q21d - 4× followed by paclitaxel (175 mg/m2) d1, q21d - 4× +/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first epirubicin dose (day 1) to 14 days after the last dose of paclitaxel<br>|
| Experimental: EC followed by paclitaxel +/- darbepoetin<br>Epirubicin (150 mg/m2) d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg, subcutaneous injection on day 2 after epirubicin and/or paclitaxel and secondary prophylactic dose after CMF +/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first dose of epirubicin (day 1) until 14 days after the last dose of CMF | Drug: Epirubicin, Cyclophosphamide, Paclitaxel, dabepoetin alfa<br>* Epirubicin (150 mg/m2) d1, q14d - 3× followed by paclitaxel (225 mg/m2) d1, q14d - 3×, followed by CMF d1/d8, q28d - 3× Obligatory pegfilgratim 6 mg, subcutaneous injection on day 2 after epirubicin and/or paclitaxel and secondary prophylactic dose after CMF +/- Darbepoetin alfa 1 × 4.5 μg/kg of body weight every two weeks with the start of the first dose of epirubicin (day 1) until 14 days after the last dose of CMF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse-free survival time and overall survival |  | 2007 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, neoadjuvant therapy, pCR rates