Preoperative Epirubicin Paclitaxel Aranesp Study (PREPARE)

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Epirubicin, paclitaxel, cyclophosphamide, Methotrexate, 5 FU, darbepoetin alfa; Drug: Epirubicin, Cyclophosphamide, Paclitaxel, dabepoetin alfa

• Registration Number: NCT00544232
• Lead Sponsor: German Breast Group

Brief Summary

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

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

Study Timeline

• Study Start: 2002-08
• Primary Completion: 2006-09
• Study Completion: 2006-09
• Study First Submitted: 2007-10-15
• Study First Submitted QC: 2007-10-15
• Study First Posted: 2007-10-16
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-12
• Last Update Posted: 2016-02-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 720

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
epirubicin, paclitaxel and CMF +/- darbepoetin	Epirubicin, paclitaxel, cyclophosphamide, Methotrexate, 5 FU, darbepoetin alfa	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
EC followed by paclitaxel +/- darbepoetin	Epirubicin, Cyclophosphamide, Paclitaxel, dabepoetin alfa	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

Primary Outcome Measures

Name	Time	Method
Relapse-free survival time and overall survival	2007