Epirubicin or Not in Patients With TOP2A (Topoisomerase (DNA) II Alpha (170kD)) Normal Early Breast Cancer (READ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00689156

Recruitment Status : Completed

First Posted : June 3, 2008

Last Update Posted : April 5, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Fonden Til Fremme af Klinisk- Eksperimentel Cancerforskning

Sanofi

Dako

Information provided by (Responsible Party):

Bent Ejlertsen, Danish Breast Cancer Cooperative Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: Epirubicin, cyclophosphamide and docetaxel Drug: docetaxel, cyclophosphamide	Phase 3

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.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2015 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (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
Study Start Date :	June 2008
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	January 2013

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Cyclophosphamide Epirubicin hydrochloride Epirubicin Docetaxel

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

IDFS; invasive disease-free survival [ Time Frame: Within 10-yeras ]

Secondary Outcome Measures :

Overall survival [ Time Frame: Life-long observation ]
DDFS; distant disease-free survival [ Time Frame: Within 10-years ]
Serious adverse events [ Time Frame: Within 10-years ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00689156

Locations

Layout table for location information

Denmark
Dept. of Oncology; Aalborg Sygehus
Aalborg, Denmark, DK-9000
Dept. of Oncology; Rigshospitalet
Copenhagen, Denmark, DK-2100
Dept. of Oncology; Sydvestjysk Sygehus Esbjerg
Esbjerg, Denmark, DK-6700
Dept. of Oncology; Herlev Hospital
Herlev, Denmark, DK-2730
Dept. of Oncology; Regionshospitalet Herning
Herning, Denmark, DK-7400
Dept. of Oncology; Nordsjællands Hospital Hillerød
Hillerød, Denmark, DK-3400
Dept. of Oncology; Sygehus Syd Næstved
Næstved, Denmark, DK-4700
Dept. of Oncology; Odense University Hospital
Odense, Denmark, DK-5000
Dept. of Oncology; Sygehus Øst Roskilde
Roskilde, Denmark, DK-4000
Dept. of internal medicine; Bornholms Hospital
Rønne, Denmark, DK-3700
Dept. of Oncology; Vejle Sygehus
Vejle, Denmark, DK-7100
Dept. of Oncology; Regionshospitalet Viborg
Viborg, Denmark, DK-8800
Dept. of Oncology; Århus Sygehus
Århus, Denmark, DK-8000

Sponsors and Collaborators

Danish Breast Cancer Cooperative Group

Fonden Til Fremme af Klinisk- Eksperimentel Cancerforskning

Sanofi

Dako

Investigators

Layout table for investigator information

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:

Moller 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. doi: 10.1080/02841860802059259.

Knoop AS, Knudsen H, Balslev E, Rasmussen BB, Overgaard J, Nielsen KV, Schonau A, Gunnarsdottir 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. doi: 10.1200/JCO.2005.11.007. Erratum In: J Clin Oncol. 2006 Feb 20;24(6):1015.

Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Hojris I, Ewertz M, Balslev E, Dano H, Vestlev PM, Kenholm J, Nielsen DL, Bechmann T, Andersson M, Cold S, Nielsen HM, Maae E, Carlsen D, Mouridsen HT. Adjuvant Cyclophosphamide and Docetaxel With or Without Epirubicin for Early TOP2A-Normal Breast Cancer: DBCG 07-READ, an Open-Label, Phase III, Randomized Trial. J Clin Oncol. 2017 Aug 10;35(23):2639-2646. doi: 10.1200/JCO.2017.72.3494. Epub 2017 Jun 29.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fei F, Messina C, Slaets L, Chakiba C, Cameron D, Bogaerts J, Bonnefoi H. Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial. Eur J Cancer. 2015 Feb;51(3):301-9. doi: 10.1016/j.ejca.2014.11.023. Epub 2015 Jan 8.

Eckhoff L, Knoop A, Jensen MB, Ewertz M. Persistence of docetaxel-induced neuropathy and impact on quality of life among breast cancer survivors. Eur J Cancer. 2015 Feb;51(3):292-300. doi: 10.1016/j.ejca.2014.11.024. Epub 2014 Dec 22.

Layout table for additonal information

Responsible Party:	Bent Ejlertsen, Professor, MD, PhD, Danish Breast Cancer Cooperative Group
ClinicalTrials.gov Identifier:	NCT00689156
Other Study ID Numbers:	DBCG 07-READ
First Posted:	June 3, 2008 Key Record Dates
Last Update Posted:	April 5, 2018
Last Verified:	January 2013

Keywords provided by Bent Ejlertsen, Danish Breast Cancer Cooperative Group:


Epirubicin docetaxel Adjuvant chemotherapy DNA Topoisomerases, Type II

Additional relevant MeSH terms:

Layout table for MeSH terms

Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Docetaxel Epirubicin Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents	Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Tubulin Modulators Antimitotic Agents Mitosis Modulators Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

To Top