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

Danish Breast Cancer Cooperative Group (DBCG)

Status and phase: Completed; Phase 3

Conditions: Breast Neoplasms

Treatments: Drug: docetaxel, cyclophosphamide; Drug: Epirubicin, cyclophosphamide and docetaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00689156

DBCG 07-READ

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,015 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,015 participants in 2 patient groups

Regimen 1

Active Comparator group

Description:

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

Treatment:

Drug: Epirubicin, cyclophosphamide and docetaxel

Regimen 2

Experimental group

Description:

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

Treatment:

Drug: docetaxel, cyclophosphamide