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

Breast Neoplasms Clinical Trial

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Official title:

Randomized Trial of Epirubicin and Cyclophosphamide Followed by Docetaxel Against Docetaxel and Cyclophosphamide in Patients With TOP2A Normal Early Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00689156
• Other study ID #: DBCG 07-READ
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2008
• Last updated: April 3, 2018
• Start date: June 2008
• Est. completion date: January 2013

Study information

• Verified date: January 2013
• Source: Danish Breast Cancer Cooperative Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2015
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Trial Population:

1. Younger than 35, but at least 18 years of age

2. Hormone receptor-negative tumor (ER- and PgR-negative) and 35 to 75 years of age.

3. 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:

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.

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Denmark	Dept. of Oncology; Aalborg Sygehus	Aalborg
Denmark	Dept. of Oncology; Århus Sygehus	Århus
Denmark	Dept. of Oncology; Rigshospitalet	Copenhagen
Denmark	Dept. of Oncology; Sydvestjysk Sygehus Esbjerg	Esbjerg
Denmark	Dept. of Oncology; Herlev Hospital	Herlev
Denmark	Dept. of Oncology; Regionshospitalet Herning	Herning
Denmark	Dept. of Oncology; Nordsjællands Hospital Hillerød	Hillerød
Denmark	Dept. of Oncology; Sygehus Syd Næstved	Næstved
Denmark	Dept. of Oncology; Odense University Hospital	Odense
Denmark	Dept. of internal medicine; Bornholms Hospital	Rønne
Denmark	Dept. of Oncology; Sygehus Øst Roskilde	Roskilde
Denmark	Dept. of Oncology; Vejle Sygehus	Vejle
Denmark	Dept. of Oncology; Regionshospitalet Viborg	Viborg

Sponsors (4)

Lead Sponsor	Collaborator
Danish Breast Cancer Cooperative Group	Dako, Fonden Til Fremme af Klinisk- Eksperimentel Cancerforskning, Sanofi

Country where clinical trial is conducted

Denmark, 

References & Publications (3)

Ejlertsen B, Tuxen MK, Jakobsen EH, Jensen MB, Knoop AS, Højris I, Ewertz M, Balslev E, Danø 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. — View Citation

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. — View Citation

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. doi: 10.1080/02841860802059259. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IDFS; invasive disease-free survival		Within 10-yeras
Secondary	Overall survival		Life-long observation
Secondary	DDFS; distant disease-free survival		Within 10-years
Secondary	Serious adverse events		Within 10-years

External Links

•   Danish Breast Cancer Cooperative Group