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]
18 Years
N/A
Female
Breast Cancer
Trial Information
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]
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of pathologic complete remission (pCR) after neoadjuvant therapy comprising docetaxel and trastuzumab (Herceptin®) in women with locally advanced, HER2-positive, operable breast cancer
Safety Issue:
No
Principal Investigator
Stefan Paepke, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Technische Universität München
Authority:
United States: Federal Government
Study ID:
CDR0000516034
NCT ID:
NCT00398489
Start Date:
October 2006
Completion Date:
Related Keywords:
- Breast Cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- stage II breast cancer
- inflammatory breast cancer
- Breast Neoplasms
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