Preoperative Epirubicin Paclitaxel Aranesp Study (PREPARE)

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00544232
• Other study ID #: GBG 49
• Status: Completed
• Phase: Phase 3
• First received: October 15, 2007
• Last updated: February 12, 2016
• Start date: August 2002
• Est. completion date: September 2006

Study information

• Verified date: February 2016
• Source: German Breast Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 720
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
German Breast Group	Amgen, Bristol-Myers Squibb, Pharmacia

References & Publications (2)

Untch M, Fasching PA, Konecny GE, von Koch F, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Schuster T, Nekljudova V, Lebeau A, Loibl S, von Minckwitz G; Arbeits — View Citation

Untch M, von Minckwitz G, Konecny GE, Conrad U, Fett W, Kurzeder C, Lück HJ, Stickeler E, Urbaczyk H, Liedtke B, Beckmann MW, Salat C, Harbeck N, Müller V, Schmidt M, Hasmüller S, Lenhard M, Nekljudova V, Lebeau A, Loibl S, Fasching PA; Arbeitsgemeinschaf — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse-free survival time and overall survival		2007	No