Clinical trial NCT00689156: Epirubicin or Not in Patients With TOP2A (Topoisomerase (DNA) II Alpha (170kD)) Normal Early Breast Cancer
Official title: Randomized Trial of Epirubicin and Cyclophosphamide Followed by Docetaxel Against Docetaxel and Cyclophosphamide in Patients With TOP2A Normal Early Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Neoplasms
Keywords: Epirubicin
docetaxel
Adjuvant chemotherapy
DNA Topoisomerases, Type II
Lead sponsor: Danish Breast Cancer Cooperative Group
Sponsor class: OTHER
Collaborators: name: Fonden Til Fremme af Klinisk- Eksperimentel Cancerforskning
name: Sanofi
name: Dako
First posted: 2008-06-03
Enrollment: 2015
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 criteria: 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.

Primary outcomes:
measure: IDFS; invasive disease-free survival
timeFrame: Within 10-yeras
Secondary outcomes:
measure: Overall survival
timeFrame: Life-long observation
measure: DDFS; distant disease-free survival
timeFrame: Within 10-years
measure: Serious adverse events
timeFrame: Within 10-years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Dept. of Oncology; Aalborg Sygehus
city: Copenhagen
country: Denmark
facility: Dept. of Oncology; Rigshospitalet
city: Esbjerg
country: Denmark
facility: Dept. of Oncology; Sydvestjysk Sygehus Esbjerg
city: Herlev
country: Denmark
facility: Dept. of Oncology; Herlev Hospital
city: Herning
country: Denmark
facility: Dept. of Oncology; Regionshospitalet Herning
city: Hillerød
country: Denmark
facility: Dept. of Oncology; Nordsjællands Hospital Hillerød
city: Næstved
country: Denmark
facility: Dept. of Oncology; Sygehus Syd Næstved
city: Odense
country: Denmark
facility: Dept. of Oncology; Odense University Hospital
city: Roskilde
country: Denmark
facility: Dept. of Oncology; Sygehus Øst Roskilde
city: Rønne
country: Denmark
facility: Dept. of internal medicine; Bornholms Hospital
city: Vejle
country: Denmark
facility: Dept. of Oncology; Vejle Sygehus
city: Viborg
country: Denmark
facility: Dept. of Oncology; Regionshospitalet Viborg
city: Århus
country: Denmark
facility: Dept. of Oncology; Århus Sygehus
Study officials:
affiliation: Rigshospitalet, Denmark
name: Bent Ejlertsen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Henning T. Mouridsen, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.