Epirubicin and Vinorelbine in Treating Patients With Stage II, Stage III, or Stage IV Breast Cancer

Study Overview
=================
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.

Official Title
-----------------
A Phase II Trial of Sequential Epirubicin/Vinorelbine in Patients With Advanced Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: epirubicin
* Drug: vinorelbine


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential epirubicin/vinorelbine<br>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. | Drug: epirubicin<br>* Epirubicin (100 mg/m2) will be given on Day 1<br>* Other names: epirubicin hydrochloride;Drug: vinorelbine<br>* Vinorelbine (18.75 mg/m2) will be given on Days 3 and 17.<br>* Other names: vinorelbine ditartrate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IV breast cancer, male breast cancer