Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IV breast cancer, male breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as epirubicin and vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving epirubicin together with vinorelbine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving epirubicin together with vinorelbine works in treating patients with stage II, stage III, or stage IV breast cancer.
Detailed description
OBJECTIVES: * Assess the efficacy of sequential use of epirubicin hydrochloride followed by vinorelbine ditartrate in patients with stage IIB, IIIA, IIIB, or IV breast cancer. * Measure the biological response to this regimen in sequential tumor biopsies and peripheral mononuclear cells from these patients. * Correlate tumor response with changes in the gene expression of microtubule-associated protein 4. OUTLINE: Patients receive epirubicin hydrochloride IV on day 1 and vinorelbine ditartrate IV over 6-10 minutes on days 3 and 17. Patients also receive filgrastim (G-CSF) subcutaneously on days 4-14 or pegfilgrastim IV on day 4. For patients with stage IIB (T3, N0), IIIA, or IIIB disease, treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. For patients with stage IV disease, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and after course 1 for research studies. Patients with accessible tumor for biopsy undergo sequential biopsies and core needle biopsies at baseline and after course 1. Tumor tissue samples are used for determination of p53 status by western blot analysis, immunohistochemistry, and DNA sequencing. Microtubule-associated protein 4, p53, and p21/WAF1 expression is analyzed by western blotting. After completion of study treatment, patients are followed for 1 month. PROJECTED ACCRUAL: A total of 46 patients will be accrued for this study.
Interventions
DRUGepirubicin
Epirubicin (100 mg/m2) will be given on Day 1
DRUGvinorelbine
Vinorelbine (18.75 mg/m2) will be given on Days 3 and 17.
Sponsors
National Cancer Institute (NCI)
University of Medicine and Dentistry of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed stage IIB (T3, N0), IIIA, IIIB, or IV breast carcinoma * Original tumor must be available for analysis of p53 status * Measurable disease, defined as any lesion that can be accurately measured in ≥ 1 dimension with longest diameter ≥ 20 mm using conventional techniques OR ≥ 10 mm with spiral CT scan * Stage IIIB disease will be assessed by clinical exam (monitoring skin changes as well as tumor size) * No visceral crisis (lymphangitic pulmonary spread, or liver or marrow replacement sufficient to cause significant organ dysfunction) * No untreated CNS metastases * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Menopausal status not specified * ECOG performance status 0-2 * Life expectancy ≥ 8 weeks * Absolute neutrophil count ≥ 1,000/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 10 g/dL * Bilirubin normal * AST ≤ 3 times normal (≤ 5 times normal if liver metastases are present) * Creatinine ≤ 1.5 mg/dL * Ejection fraction ≥ lower limit of normal by MUGA scan or ECG * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective nonhormonal contraception * No other malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer * No pre-existing disease (i.e., cardiac, pulmonary, neurologic, or other disease) that the investigator judges to be clinically significant * No active infectious process, severe malnutrition, or intractable emesis PRIOR CONCURRENT THERAPY: * Recovered from all prior therapy * At least 3 weeks since prior radiotherapy * At least 3 weeks since prior chemotherapy * Maximum prior doxorubicin hydrochloride dose must be ≤ 300 mg/m² OR equivalent anthracycline (epirubicin hydrochloride) dose must be ≤ 540 mg/m² OR calculated total anthracycline dose must be ≤ 540 mg/m² (determined as 1.8 times total doxorubicin hydrochloride dose plus epirubicin hydrochloride dose) * No prior chemotherapy for metastatic disease * Prior adjuvant chemotherapy, radiotherapy, and/or hormonal therapy for breast cancer allowed * No concurrent radiotherapy except for brain metastases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy of the Sequential Use of a DNA Damaging Drug (Epirubicin) Followed by a Vinca Alkaloid (Vinorelbine) in the Treatment of Breast Cancer. | 10 years |
Secondary
| Measure | Time frame |
|---|---|
| Biological Response to Epirubicin and Vinorelbine Administered in Patients With Breast Cancer in Sequential Tumor Biopsies and Peripheral Blood Mononuclear Cells. | 10 years |
| Correlate Tumor Response With Changes in the Gene Expression of Microtubule Associated Protein 4 (MAP4). | 10 years |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Cancer Institute of New Jersey (a comprehensive cancer center) from June 2003 through May 2009.
Participants by arm
| Arm | Count |
|---|---|
| Sequential Epirubicin/Vinorelbine For patients with stage IIB (T3N0), IIIA, or IIIB breast cancer, epirubicin and vinorelbine will be administered for up to 5 cycles. For patients with stage IV breast cancer, epirubicin and vinorelbine will be administered as long as there is evidence of continued response or stable disease and no evidence of cardiac or other serious toxicities.
epirubicin : Epirubicin (100 mg/m2) will be given on Day 1
vinorelbine : Vinorelbine (18.75 mg/m2) will be given on Days 3 and 17. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Initiated Cycle 1 Day 1 only | 1 |
Baseline characteristics
| Characteristic | Sequential Epirubicin/Vinorelbine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 50.0 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 14 / 31 |
Outcome results
Primary
Efficacy of the Sequential Use of a DNA Damaging Drug (Epirubicin) Followed by a Vinca Alkaloid (Vinorelbine) in the Treatment of Breast Cancer.
Time frame: 10 years
Population: Study was closed prematurely and insufficient data was collected.
Secondary
Biological Response to Epirubicin and Vinorelbine Administered in Patients With Breast Cancer in Sequential Tumor Biopsies and Peripheral Blood Mononuclear Cells.
Time frame: 10 years
Population: Study was closed prematurely and insufficient data was collected.
Secondary
Correlate Tumor Response With Changes in the Gene Expression of Microtubule Associated Protein 4 (MAP4).
Time frame: 10 years
Population: Study was closed prematurely and insufficient data was collected.