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

NCT ID: NCT00689156

Last Updated: 2018-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2015 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2013-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Epirubicin, cyclophosphamide and docetaxel

Intervention Type DRUG

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

Regimen 2

Docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times six

Group Type EXPERIMENTAL

docetaxel, cyclophosphamide

Intervention Type DRUG

Docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times six

Interventions

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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

Intervention Type DRUG

docetaxel, cyclophosphamide

Docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 intravenously day 1 every 3 weeks times six

Intervention Type DRUG

Other Intervention Names

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Ellence Taxotere Taxotere

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

1. Pregnancy or breast-feeding
2. Earlier medical cancer treatment, including docetaxel, epirubicin or cyclophosphamide.
3. Distant metastases or bilateral breast cancer (excluded after checking by means of chest radiography, bilateral mammography and normal blood samples as a minimum).
4. 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.
5. Comorbidity score \> 3 (patients with a score of 1-2 start at dose level -1).
6. Treatment with a non-approved product or test product in the latest 30 days.
7. Known severe hypersensitivity to docetaxel, epirubicin or cyclophosphamide or auxiliary agents in these products.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Fonden Til Fremme af Klinisk- Eksperimentel Cancerforskning

OTHER

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role collaborator

Dako

INDUSTRY

Sponsor Role collaborator

Danish Breast Cancer Cooperative Group

OTHER

Sponsor Role lead

Responsible Party

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Bent Ejlertsen

Professor, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Bent Ejlertsen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Rigshospitalet, Denmark

Henning T. Mouridsen, M.D.

Role: STUDY_DIRECTOR

Rigshospitalet, Denmark

Locations

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Dept. of Oncology; Aalborg Sygehus

Aalborg, , Denmark

Site Status

Dept. of Oncology; Århus Sygehus

Aarhus, , Denmark

Site Status

Dept. of Oncology; Rigshospitalet

Copenhagen, , Denmark

Site Status

Dept. of Oncology; Sydvestjysk Sygehus Esbjerg

Esbjerg, , Denmark

Site Status

Dept. of Oncology; Herlev Hospital

Herlev, , Denmark

Site Status

Dept. of Oncology; Regionshospitalet Herning

Herning, , Denmark

Site Status

Dept. of Oncology; Nordsjællands Hospital Hillerød

Hillerød, , Denmark

Site Status

Dept. of Oncology; Sygehus Syd Næstved

Næstved, , Denmark

Site Status

Dept. of Oncology; Odense University Hospital

Odense, , Denmark

Site Status

Dept. of Oncology; Sygehus Øst Roskilde

Roskilde, , Denmark

Site Status

Dept. of internal medicine; Bornholms Hospital

Rønne, , Denmark

Site Status

Dept. of Oncology; Vejle Sygehus

Vejle, , Denmark

Site Status

Dept. of Oncology; Regionshospitalet Viborg

Viborg, , Denmark

Site Status

Countries

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Denmark

References

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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.

Reference Type BACKGROUND
PMID: 18465317 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16234514 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28661759 (View on PubMed)

Jensen MB, Balslev E, Knoop AS, Tuxen MK, Hojris I, Jakobsen EH, Cold S, Dano H, Glavicic V, Kenholm J, Ejlertsen B. Adjuvant Docetaxel and Cyclophosphamide With or Without Epirubicin for Early Breast Cancer: Final Analysis of the Randomized DBCG 07-READ Trial. J Clin Oncol. 2025 Feb;43(4):373-380. doi: 10.1200/JCO.24.00836. Epub 2024 Oct 23.

Reference Type DERIVED
PMID: 39442040 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25578377 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25541155 (View on PubMed)

Related Links

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http://www.dbcg.dk

Danish Breast Cancer Cooperative Group

Other Identifiers

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DBCG 07-READ

Identifier Type: -

Identifier Source: org_study_id

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