Phase II Study of Trastuzumab (Herceptin) and Capecitabine (Xeloda) in Women With Taxanes and Anthracyclines Refractory Metastatic Breast Cancer and HER2 Over-Expression
20 Years
75 Years
Female
Breast Cancer
Trial Information
Phase II Study of Trastuzumab (Herceptin) and Capecitabine (Xeloda) in Women With Taxanes and Anthracyclines Refractory Metastatic Breast Cancer and HER2 Over-Expression
OBJECTIVES:
Primary
- Determine the median survival time and 2-year survival rate in women with taxane- and
anthracycline-refractory HER2/neu-overexpressing metastatic breast cancer treated with
trastuzumab (Herceptin®) and capecitabine.
Secondary
- Determine the progression-free survival of patients treated with this regimen.
- Determine the response rate in patients treated with this regimen.
- Determine the clinical benefit rate of this regimen in these patients.
- Determine the safety profile of this regimen in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment
with trastuzumab (Herceptin®) (yes vs no), HER2/neu status (3+ by immunohistochemistry vs
positive by fluorescence in situ hybridization), and class of refractory disease (primary vs
secondary vs treatment discontinuation due to adverse events).
Patients receive oral capecitabine once daily on days 1-21 and trastuzumab IV on days 1, 8,
15, and 22. Treatment repeats every 28 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 2 years.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study within 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed breast cancer
- Metastatic disease
- Patients with only bone metastases are not eligible
- Refractory disease, defined as disease progression, drug-related adverse reaction, or
disease relapse during or within 12 months after completion of paclitaxel or
docetaxel AND doxorubicin or epirubicin administered in the neoadjuvant, adjuvant, or
metastatic setting
- Total neoadjuvant or adjuvant taxane dose > 700 mg/m^2 for paclitaxel or > 240
mg/m^2 for docetaxel
- Total taxane dose > 350 mg/m^2 for paclitaxel or > 120 mg/m^2 for docetaxel in
the metastatic setting
- Total neoadjuvant or adjuvant anthracycline dose > 240 mg/m^2 for doxorubicin or
epirubicin
- Total anthracycline dose > 120 mg/m^2 for doxorubicin or epirubicin in the
metastatic setting
- HER2/neu overexpression
- 3+ by immunohistochemistry or positive by fluorescence in situ hybridization
- No symptomatic brain metastases
- No pleural or pericardial effusion or ascites
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 20 to 75
Sex
- Female
Menopausal status
- Not specified
Performance status
- ECOG 0-2
Life expectancy
- At least 3 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 9.0 g/dL
Hepatic
- SGOT or SGPT ≤ 2.0 times upper limit of normal (ULN) (< 3.0 times ULN for patients
with liver metastases)
- Alkaline phosphatase ≤ 2.5 times ULN
- Bilirubin ≤ 1.5 mg/dL
Renal
- Creatinine ≤ 1.2 mg/dL
Cardiovascular
- LVEF > 50%
Pulmonary
- No interstitial pneumonia with pulmonary fibrosis
Other
- No history of hypersensitivity reactions
- No serious, uncontrolled infection
- No other malignancy
- Not pregnant or nursing
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior trastuzumab (Herceptin®) for metastatic disease allowed
Chemotherapy
- See Disease Characteristics
- No prior capecitabine
- At least 2 weeks since prior antimetabolites for metastatic disease
- At least 4 weeks since prior alkylating agents, carcinostatic antibiotics, or other
carcinostatic agents
Endocrine therapy
- At least 4 weeks since prior goserelin or leuprolide for metastatic disease
- At least 2 weeks since prior oral endocrine agents for metastatic disease
- No concurrent endocrine therapy
Radiotherapy
- No prior radiotherapy to target lesions
- At least 4 weeks since prior radiotherapy
- No concurrent radiotherapy, including radiotherapy for brain metastases
Surgery
- Not specified
Other
- Concurrent bisphosphonates for bone metastases allowed
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Median survival and 2-year survival rate as measured by the Kaplan-Meier method 2 years after completion of study treatment
Safety Issue:
No
Principal Investigator
Noriaki Ohuchi, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Tohoku University
Authority:
United States: Federal Government
Study ID:
TUGSM-UHA-BC03-01
NCT ID:
NCT00107393
Start Date:
June 2003
Completion Date:
November 2008
Related Keywords:
- Breast Cancer
- recurrent breast cancer
- stage IV breast cancer
- Breast Neoplasms
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