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

Neoadjuvant Epirubicin/Cyclophosphamide Followed by Docetaxel Combined With Trastuzumab for the Patients With HER-Positive Advanced Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: docetaxel; Procedure: neoadjuvant therapy; Procedure: conventional surgery; Biological: trastuzumab; Drug: epirubicin hydrochloride

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 173-8605
    • Teikyo University School of Medicine
  • Ehime
    • Matsuyama-shi, Ehime, Japan, 791-0288
      • Shikoku Cancer Center
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Kyushu Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: HER2 over-expressing primary breast cancer group; 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Pathological complete response is assessed in surgical resected specimens of primary tumor from patients who underwent a primary radical surgery in this study.	Whitin the first 7-28 days after the last administration of neoadjuvant therapy of trastuzumab

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Clinical response is assessed as overall response in target lesion of primary tumor from 7 days after the last administration of neoadjuvant therapy of Trastuzumab until surgery.	From 7 days after the last adoministration of neosdjuvant therapy of Trastuzumab until surgery.
Pathological response of axillary lymph nodes	Pathological response of axillary lymph nodes is assessed in surgical specimens of primary tumor from patients who underwent a primary radical surgery in this study.	Whitin the first 7-28 days after the last administration of neoadjuvant therapy of trastuzumab.
Recurrence-free survival	Recurrence-free survival is defined as time from date of enrollment until date of recurrence or death from any cause, whichever comes first.	8 years
Overall survival	Overall survival is defined as time from date of enrollment until date of death from any cause.	8 years
Adverse event	Types and severities of adverse events from date of starting protocol treatment until 30 days after date of finishing the treatment are evaluated according to Japanese version of the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) by Translational Research Informatics Center.	70 months

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Investigators: Study Chair: Tadashi Ikeda, MD, Teikyo University

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 19, 2006
• First Submitted That Met QC Criteria: September 19, 2006
• First Posted (Estimate): September 21, 2006

Study Record Updates

• Last Update Posted (Estimate): September 28, 2016
• Last Update Submitted That Met QC Criteria: September 27, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Trastuzumab; Epirubicin
• Other Study ID Numbers: CDR0000496448; TUSM-BRI-BC04-01