Epirubicin or Not in Patients With TOP2A (Topoisomerase (DNA) II Alpha (170kD)) Normal Early Breast Cancer - Full Text View

Sponsor:	Danish Breast Cancer Cooperative Group
Collaborators:	Fonden til fremme af klinisk eksperimentel cancerforskning vedrørende c. mammae Sanofi-Aventis Dako
Information provided by:	Danish Breast Cancer Cooperative Group
ClinicalTrials.gov Identifier:	NCT00689156

Purpose

The Danish Breast Cancer Cooperative Group (DBCG) wishes to clarify if recurrence-free and overall life expectancy is longer after docetaxel and cyclophosphamide compared to epirubicin and cyclophosphamide followed by docetaxel in patients with TOP2A normal and operable breast cancer.

Condition	Intervention	Phase
Breast Neoplasms	Drug: Epirubicin, cyclophosphamide and docetaxel Drug: docetaxel, cyclophosphamide	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Randomized Trial of Epirubicin and Cyclophosphamide Followed by Docetaxel Against Docetaxel and Cyclophosphamide in Patients With TOP2A Normal Early Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Epirubicin hydrochloride Epirubicin Docetaxel

U.S. FDA Resources

Further study details as provided by Danish Breast Cancer Cooperative Group:

Primary Outcome Measures:

IDFS; invasive disease-free survival [ Time Frame: Within 10-yeras ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Time Frame: Life-long observation ] [ Designated as safety issue: No ]
DDFS; distant disease-free survival [ Time Frame: Within 10-years ] [ Designated as safety issue: No ]
Serious adverse events [ Time Frame: Within 10-years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1932
Study Start Date:	June 2008
Estimated Study Completion Date:	January 2022
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Regimen 1 Epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times three followed by docetaxel 100 mg/m2 intravenously day 1 every 3 weeks times three	Drug: Epirubicin, cyclophosphamide and docetaxel Epirubicin 90 mg/m2 iv day 1 every 3 weeks plus Cyclophosphamide 600 mg/m2 iv day 1 every 3 weeks times 3 followed by Docetaxel 100 mg/m2 iv day 1 every 3 weeks times 3 Other Names: Ellence Taxotere
Experimental: Regimen 2 Docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times six	Drug: docetaxel, cyclophosphamide Docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times six Other Name: Taxotere

Detailed Description:

In DBCG trial 89D we in more than 1,200 patients showed that substitution in CMF chemotherapy of methotrexate with epirubicin improves survival for patients with primary and operable breast cancer. In a retrospective evaluation we have also shown that approximately 20% of all patients in 89D have tumors with numerical changes of the TOP2A gene, and that only patients with abnormal TOP2A benefit from epirubicin. In the current trial the DBCG wishes to clarify if recurrence-free and overall life expectancy is longer after docetaxel and cyclophosphamide compared to epirubicin and cyclophosphamide followed by docetaxel in patients with TOP2A normal and operable breast cancer.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Trial Population:

Younger than 35, but at least 18 years of age
Hormone receptor-negative tumor (ER- and PgR-negative) and 35 to 75 years of age.
Hormone receptor-positive tumor, 35 to 59 years of age and presenting at least one of the following characteristics: spread to lymph nodes, tumor > 2 cm, degree of malignancy II-III or HER2-positive.

Inclusion Criteria:

Signed informed consent
Histologically confirmed invasive breast carcinoma which has been micro-radical removed by breast preserving surgery or mastectomy according to DBCG's guideline
TOP2A normal tumor (score of 0.8 - 2.0)

Exclusion Criteria:

Pregnancy or breast-feeding
Earlier medical cancer treatment, including docetaxel, epirubicin or cyclophosphamide.
Distant metastases or bilateral breast cancer (excluded after checking by means of chest radiography, bilateral mammography and normal blood samples as a minimum).
Other active, malign disease in the latest 5 years, except for adequately treated and cured carcinoma in situ cervices uteri or non-melanoma skin cancer.
Comorbidity score > 3 (patients with a score of 1-2 start at dose level -1).
Treatment with a non-approved product or test product in the latest 30 days.
Known severe hypersensitivity to docetaxel, epirubicin or cyclophosphamide or auxiliary agents in these products.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00689156

Contacts

Contact: Bent Ejlertsen, M.D.	45-3545-5088	ejlertsen@rh.dk
Contact: Henning T. Mouridsen, M.D.	45-3445-4776	mou@dbcg.dk

Locations

Denmark
Dept. of Oncology; Aalborg Sygehus	Active, not recruiting
Aalborg, Denmark, DK-9000
Dept. of Oncology; Rigshospitalet	Recruiting
Copenhagen, Denmark, DK-2100
Contact: Bent Ejlertsen, M.D. 45-3545-5088 ejlertsen@rh.dk
Dept. of Oncology; Sydvestjysk Sygehus Esbjerg	Recruiting
Esbjerg, Denmark, DK-6700
Contact: Brita B. Jensen, M.D. bbje@ribeamt.dk
Dept. of Oncology; Herlev Hospital	Recruiting
Herlev, Denmark, DK-2730
Contact: Gosia Tuxen, M.D. GOSTUX01@heh.regionh.dk
Dept. of Oncology; Regionshospitalet Herning	Recruiting
Herning, Denmark, DK-7400
Contact: Knud A. Møller, M.D. heckam@ringamt.dk
Dept. of Oncology; Nordsjællands Hospital Hillerød	Recruiting
Hillerød, Denmark, DK-3400
Contact: Mogens Hansen, M.D. moha@noh.regionh.dk
Dept. of Oncology; Sygehus Syd Næstved	Recruiting
Næstved, Denmark, DK-4700
Contact: Preben Philip, M.D. prebenphilip@newmail.dk
Dept. of Oncology; Odense University Hospital	Recruiting
Odense, Denmark, DK-5000
Contact: Ann S. Knoop, M.D. Ann.Knoop@ouh.regionsyddanmark.dk
Dept. of Oncology; Sygehus Øst Roskilde	Recruiting
Roskilde, Denmark, DK-4000
Contact: Peter G. Sørensen, M.D. rspgr@ra.dk
Dept. of internal medicine; Bornholms Hospital	Recruiting
Rønne, Denmark, DK-3700
Contact: Ditte Nielsen, M.D. ditte.nielsen@bcsygehus.dk
Dept. of Oncology; Vejle Sygehus	Recruiting
Vejle, Denmark, DK-7100
Contact: Erik H. Jakobsen, M.D. erik.hugger.jakobsen@vgs.regionsyddanmark.dk
Dept. of Oncology; Regionshospitalet Viborg	Recruiting
Viborg, Denmark, DK-8800
Contact: Vera Haahr, M.D. vera.haahr@sygehusviborg.dk
Dept. of Oncology; Århus Sygehus	Recruiting
Århus, Denmark, DK-8000
Contact: Inger Højris, M.D. ihojr@as.aaa.dk

Sponsors and Collaborators

Danish Breast Cancer Cooperative Group

Fonden til fremme af klinisk eksperimentel cancerforskning vedrørende c. mammae

Sanofi-Aventis

Dako

Investigators

Principal Investigator:	Bent Ejlertsen, M.D.	Rigshospitalet, Denmark
Study Director:	Henning T. Mouridsen, M.D.	Rigshospitalet, Denmark

More Information

Additional Information:

Danish Breast Cancer Cooperative Group This link exits the ClinicalTrials.gov site

Publications:

Møller S, Jensen MB, Ejlertsen B, Bjerre KD, Larsen M, Hansen HB, Christiansen P, Mouridsen HT; Danish Breast Cancer Cooperative Group. The clinical database and the treatment guidelines of the Danish Breast Cancer Cooperative Group (DBCG); its 30-years experience and future promise. Acta Oncol. 2008;47(4):506-24.

Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdóttir K, Olsen KE, Mouridsen H, Ejlertsen B; Danish Breast Cancer Cooperative Group. retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol. 2005 Oct 20;23(30):7483-90. Erratum in: J Clin Oncol. 2006 Feb 20;24(6):1015.

Responsible Party:	Bent Ejlertsen, M.D., Ph.D., Dept. of Oncology, Bldg. 4262 Rigshospitalet, Copenhagen
ClinicalTrials.gov Identifier:	NCT00689156 History of Changes
Other Study ID Numbers:	DBCG 07-READ
Study First Received:	May 29, 2008
Last Updated:	June 22, 2009
Health Authority:	Denmark: Danish Medicines Agency; Denmark: Danish Dataprotection Agency; Denmark: The Danish National Committee on Biomedical Research Ethics

Keywords provided by Danish Breast Cancer Cooperative Group:

Epirubicin
docetaxel
Adjuvant chemotherapy
DNA Topoisomerases, Type II

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Cyclophosphamide
Docetaxel
Epirubicin
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on February 09, 2012