Epirubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab in Treating Women With HER2-Positive Stage III or Stage IV Breast Cancer

Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Procedure: neoadjuvant therapy; Procedure: conventional surgery; Drug: epirubicin hydrochloride; Drug: cyclophosphamide; Biological: trastuzumab; Drug: docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT00379015

CDR0000496448

TUSM-BRI-BC04-01

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy and a monoclonal antibody before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving epirubicin and cyclophosphamide followed by docetaxel and trastuzumab works in treating women with HER2-positive stage IIIB, stage IIIC, or stage IV primary breast cancer.

Full description

OBJECTIVES:

Primary

• Determine the pathological complete response in women with HER2-positive stage IIIB-IV breast cancer treated with neoadjuvant epirubicin hydrochloride and cyclophosphamide followed by docetaxel and trastuzumab (Herceptin®).

Secondary

• Determine the clinical response in patients treated with this regimen.
• Determine the recurrence-free survival of patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive epirubicin hydrochloride and cyclophosphamide in weeks 1-3. Treatment with epirubicin hydrochloride and cyclophosphamide repeats every 3 weeks for 4 courses. Patients then receive docetaxel in week 13 and trastuzumab (Herceptin®) in weeks 13-15. Treatment with docetaxel and trastuzumab repeats every 3 weeks for 4 courses.

Patients then undergo appropriate surgery. After surgery, patients with hormone receptor-positive disease receive trastuzumab once weekly and either tamoxifen with or without a luteinizing hormone-releasing hormone agonist or an aromatase inhibitor. Treatment continues for 40 weeks.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Enrollment: 38 patients

Sex: Female

Ages: 20 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of primary breast cancer

  • Stage IIIB, IIIC, or IV disease

• No inflammatory disease

• HER2 over-expressing tumor as assessed by immunohistochemistry and/or fluorescent in situ hybridization

• Hormone receptor status known

PATIENT CHARACTERISTICS:

• Female
• Menopausal status not specified
• Performance status 0-1
• WBC ≤ 10,000/mm³
• Absolute neutrophil count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.5 g/dL
• SGOT/SGPT ≤ 60 IU/L
• Bilirubin ≤ 1.5 mg/dL
• Creatinine ≤ 1.5 mg/dL
• LVEF ≥ 55%
• No signs of pneumonitis

PRIOR CONCURRENT THERAPY:

• No prior surgery except for biopsy
• No prior or concurrent chemotherapy and/or hormonal therapy
• No prior or concurrent biological therapy
• No prior or concurrent radiotherapy except postoperative radiotherapy

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

HER2 over-expressing primary breast cancer group

Experimental group

Description:

Patients receive epirubicin hydrochloride and cyclophosphamide in week 1-3. Treatment with epirubicin hydrochloride and cyclophosphamide repeats every 3 weeks for 4 courses. Patients then receive docetaxel in week 13 and trastuzumab (Herceptin®) in weeks 13-15. Treatment with docetaxel and trastuzumab repeats every 3 weeks for 4 courses. Patients then undergo appropriate surgery. After surgery, patients with hormone receptor-positive disease receive trastuzumab once weekly and either tamoxifen with or without a luteinizing hormone-releasing hormone agonist or an aromatase inhibitor. Treatment continues for 40 weeks.

Treatment:

Biological: trastuzumab

Procedure: neoadjuvant therapy

Drug: docetaxel

Procedure: conventional surgery

Drug: epirubicin hydrochloride

Drug: cyclophosphamide