Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase II trial to study the effectiveness of combining paclitaxel, carboplatin, and trastuzumab in treating women who have metastatic breast cancer that overexpresses HER2.
Detailed description
OBJECTIVES: * Compare the response rate associated with two different treatment schedules of paclitaxel, carboplatin, and trastuzumab (Herceptin) in women with overexpressed HER-2 growth factor receptor and metastatic breast cancer. (Schedule A closed to accrual effective 05/16/2003). * Compare the time to progression and median survival in patients treated with these schedules. * Compare the toxicity of these treatment schedules in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior adjuvant therapy (none vs less than 6 months vs at least 6 months), estrogen receptor (ER) status and progesterone receptor (PR) status at initial diagnosis (ER positive/PR positive or unknown vs ER positive/PR negative vs ER positive or unknown/PR negative), menopausal status (pre vs post), and performance status (0 or 1 vs 2). Patients are assigned to 1 of 2 treatment schedules. * Schedule A: Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes and then trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression. (Schedule A closed to accrual effective 05/16/2003). * Schedule B: Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 15 minutes on day 1 of weeks 1-3 and trastuzumab IV over 90 minutes immediately after carboplatin on day 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive trastuzumab IV over 30 minutes every 3 weeks until disease progression. Patients are followed every 3 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 36-92 patients (18-46 per treatment schedule) will be accrued for this study within 7-18.5 months. (Schedule A closed to accrual effective 05/16/2003).
Interventions
BIOLOGICALtrastuzumab
DRUGcarboplatin
DRUGpaclitaxel
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed metastatic adenocarcinoma of the breast * Strong overexpression of HER-2 by immunohistochemistry (3+) * 0-2+ tumors allowed if demonstrate amplification by FISH * Bidimensionally measurable disease * Brain metastasis must not represent sole site of disease * No untreated brain metastasis receiving radiotherapy * Previously treated brain metastases in continued response to radiotherapy and/or surgery for at least 2 months allowed * Hormone receptor status: * Positive or negative PATIENT CHARACTERISTICS: Age: * 18 and over Sex: * Female Menopausal status: * Not specified Performance status: * ECOG 0-2 Life expectancy: * At least 3 months Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 1.5 mg/dL * AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present) Renal: * Creatinine no greater than 1.5 times ULN Cardiovascular: * No myocardial infarction within the past 6 months * No congestive heart failure or unstable angina * No clinically significant pericardial effusion or arrhythmia Other: * No other invasive malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No active uncontrolled infection * No prior allergic reaction to Cremophor EL, anesthetics, or muscle relaxants * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * No concurrent filgrastim (G-CSF) Chemotherapy: * Prior adjuvant chemotherapy allowed * Prior taxane therapy allowed * No prior cisplatin or carboplatin * No prior chemotherapy for metastatic disease Endocrine therapy: * Not specified Radiotherapy: * See Disease Characteristics * No prior radiotherapy to more than 25% of marrow * At least 4 weeks since prior radiotherapy * No concurrent radiotherapy Surgery: * See Disease Characteristics * At least 4 weeks since prior surgery and recovered Other: * At least 7 days since prior parenteral antibiotics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| response rate | Up to 5 years |
Secondary
| Measure | Time frame |
|---|---|
| time to progression | Up to 5 years |
| median survival | Up to 5 years |
Countries
Canada, United States
Outcome results
None listed