Docetaxel, Epirubicin, and Cyclophosphamide With or Without Trastuzumab in Treating Women With Locally Advanced Breast Cancer That Can Be Removed By Surgery

Sponsor

Technische Universität München (Other)

Overall Status

Unknown status

CT.gov ID

NCT00398489

Collaborator

(none)

Enrollment

Locations

18.8

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, epirubicin, and cyclophosphamide, 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 with or without monoclonal antibody therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving docetaxel, epirubicin, and cyclophosphamide with or without trastuzumab works in treating women with locally advanced breast cancer that can be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab Drug: anastrozole Drug: cyclophosphamide Drug: docetaxel Drug: epirubicin hydrochloride Drug: goserelin acetate Drug: tamoxifen citrate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the efficacy of neoadjuvant therapy comprising docetaxel and trastuzumab (Herceptin®) and adjuvant therapy comprising epirubicin hydrochloride, cyclophosphamide, and trastuzumab (Herceptin®) followed by radiotherapy in women with locally advanced, HER2-positive, operable breast cancer.
Determine the efficacy of neoadjuvant therapy with docetaxel and adjuvant therapy comprising epirubicin hydrochloride and cyclophosphamide followed by radiotherapy in women with locally advanced, HER2-negative, operable breast cancer.

OUTLINE: This is an open-label, prospective, multicenter study. Patients are stratified according to HER2 status (positive vs negative).

Neoadjuvant therapy:
Stratum 1 (HER2-positive disease): Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, and 15 and docetaxel IV over 60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity
Stratum 2 (HER2-negative disease): Patients receive docetaxel IV alone as in stratum 1.
Surgery: All patients undergo surgery in week 19.
Adjuvant therapy: Beginning within 2 weeks after surgery, patients receive adjuvant therapy.
Stratum 1 (HER2-positive disease): Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, and 15, epirubicin hydrochloride IV over 30 minutes on day 2, and cyclophosphamide IV over 30 minutes on day 2. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV alone every 3 weeks until week 52.
Stratum 2 (HER2-negative disease): Patients receive epirubicin hydrochloride and cyclophosphamide as in stratum 1.
Radiotherapy: Patients who undergo breast conserving surgery or patients who undergo mastectomy with ypN positive lymph nodes (i.e., > 4 positive lymph nodes) or ypT3 tumor (i.e., tumor size > 4 cm) undergo radiotherapy, beginning in approximately week 31 and continuing until up to week 38.
Adjuvant endocrine therapy: Patients with estrogen receptor- or progesterone receptor-positive disease receive adjuvant endocrine therapy beginning in approximately week 31. Premenopausal patients ≤ 40 years of age receive goserelin for 2-3 years and tamoxifen citrate for 5 years.Premenopausal patients > 40 years of age receive tamoxifen citrate for 5 years. Postmenopausal patients receive anastrozole for 5 years years.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 94 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

94 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of Response Rate to Pre-Operative Docetaxel + Herceptin Study Part A and Docetaxel Study Part B in Locally Advanced Breast Cancer Patients, Stratified by HER2-Status Trial - PHASE II [(Herceptin Docetaxel Neoadjuvant) HEDON]

Study Start Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Rate of pathologic complete remission (pCR) after neoadjuvant therapy comprising docetaxel and trastuzumab (Herceptin®) in women with locally advanced, HER2-positive, operable breast cancer []
Rate of pCR after neoadjuvant docetaxel in women with locally advanced, HER2-negative, operable breast cancer []
Tolerability of treatment as measured by the nature and frequency of adverse events in women with HER2-positive or HER2-negative disease []
Identification of predictive markers []

Secondary Outcome Measures

Rate of breast conserving therapy versus mastectomy in comparison to preoperative evaluation []
Correlation of clinical/sonographical response with pathological response, including lymph node status []
Rate of clinical complete remission (cCR) after neoadjuvant therapy comprising docetaxel and trastuzumab in women with locally advanced, HER2-positive, operable breast cancer []
Rate of cCR after neoadjuvant docetaxel in women with locally advanced, HER2-negative, operable breast cancer []
Disease-free survival after 2.5 and 5 years []
Overall-survival after 2.5 and 5 years []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed primary carcinoma of the breast by core biopsy
Solitaire or multifocal disease, defined as tumor manifestations within a quadrant or distance between tumor manifestations measured bilaterally < 4 cm, respectively
No multifocal primary tumor, defined as tumor manifestations in different quadrants or distance between tumor manifestations ≥ 4 cm
Locally advanced, operable disease
Primary tumor ≥ 2 cm by clinical examination or imaging (i.e., mammogram, MRI, or ultrasound)
Inflammatory breast cancer with bidimensionally measurable lesion, independent of nodal status, allowed
HER2 status meeting 1 of the following criteria:
HER2-positive disease
3+ by immunohistochemistry (IHC) and/or positive by fluorescence in situ hybridization (FISH)
HER-2 negative disease
0 or 1+ by IHC OR 2+ by IHC and negative by FISH
No distant metastases by clinical or imaging diagnosis
No prior breast cancer
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Female
Pre- or post-menopausal
ECOG performance status 0-2
Platelet count ≥ 100,000/mm^3
Neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 10 g/dL
ALT and AST ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Bilirubin normal (unless due to clearly documented Gilbert's syndrome)
Not pregnant or nursing
Negative pregnancy test (for premenopausal women or women with a postmenopausal status for < 1 year)
Fertile patients must use effective contraception
Adequate organ function for cytotoxic chemotherapy
No known hypersensitivity reaction to the study agents or incorporated substances
No known allergy or severe reactions to trastuzumab or its constituents (for patients with HER2-positive disease)
No preexisting motor or sensory neuropathy ≥ grade 2
No other invasive malignancy within the past 5 years that would preclude study compliance or affect the interpretation of study results
LVEF ≥ 55% by MUGA or echocardiography
No other serious illness or medical condition, including any of the following:
New York Heart Association class II-IV congestive heart failure
History of documented congestive heart failure
Unstable angina pectoris
Myocardial infarction within the past 12 months
Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
Clinically significant valvular heart disease
High-risk, uncontrolled arrhythmias
Dyspnea at rest due to malignant or other disease
Condition that requires supportive oxygen therapy
Active serious uncontrolled infections
Uncontrolled diabetes

PRIOR CONCURRENT THERAPY:

No prior systemic therapy for cancer
No prior trastuzumab (Herceptin^®) (for HER2-positive patients)
No other concurrent anticancer therapy
No other concurrent investigational drugs
No concurrent immunosuppressive therapy
No concurrent sex hormones
No concurrent corticosteroids unless for premedication
No concurrent bisphosphonates during active treatment with chemotherapy

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Klinikum Bayreuth	Bayreuth	Germany	D 95448
2	Universitaetsfrauenklinik - Koeln	Cologne	Germany	D-50391
3	Klinikum Deggendorf	Deggendorf	Germany	94469
4	Klinikum der Friedrich-Schiller Universitaet Jena	Jena	Germany	D-07743
5	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich	Germany	D-81675