Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more effective in treating breast cancer. PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus radiation therapy with or without trastuzumab in treating women who have breast cancer that has spread to lymph nodes in the axilla (under the arm).

Detailed Description
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OBJECTIVES: Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion. Determine survival of patients treated with these regimens. Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens. Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors. Evaluate the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts. Part I: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks. Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I. Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment. Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years. Part II: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year. Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.

Official Title
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Randomized And Multicentric Opened Phase III Study Evaluating The Concomitant Administration Of Docetaxel 75MG/M2 and Epirubicine 75MG/M2 Versus FEC 100 In Non Metastatic With Positive Lymphatic Nodes Breast Cancer Subjects, And The Sequential Addition Of Herceptin In (HER2+++) And (HER2++ And FISH+) Subjects

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Trastuzumab
* Drug: Cyclophosphamide
* Drug: docetaxel
* Drug: Epirubicin
* Drug: Fluorouracil


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast Axillary lymph node invasion (N1, N2, or N3) No cutaneous invasion No T4a or greater disease No clinically or radiologically suspected metastases No clinically or radiologically suspected contralateral lesion No deeply adherent or inflammatory disease Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days No prior breast cancer Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 to 64 Sex Female Menopausal status Not specified Performance status WHO 0-1 Life expectancy Not specified Hematopoietic WBC at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hepatic ALT and AST no greater than 1.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Bilirubin no greater than ULN Hepatitis B and hepatitis C negative No hepatic dysfunction Renal Creatinine less than 1.3 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular ECHO normal LVEF at least 50% Pulmonary FEV normal No dyspnea at rest No supplemental oxygen dependence Other Not pregnant Fertile patients must use effective contraception HIV negative No active infection No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix No contraindication to anthracycline therapy No chronic medical or psychological condition No geographic or social reason that would preclude study therapy PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 4 weeks since prior chemotherapy No other concurrent chemotherapy No contraindication to anthracycline therapy Endocrine therapy No prior hormonal therapy Radiotherapy No prior radiotherapy Surgery See Disease Characteristics Other At least 4 weeks since prior experimental therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 6 FEC<br>Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks. | Biological: Trastuzumab<br>* 8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)<br>* Other names: Herceptin;Drug: Cyclophosphamide<br>* 500 mg/m², D1 and every 3 weeks<br>Drug: Epirubicin<br>* 100 mg/m², D1 and every 3 weeks<br>* Other names: epirubicin hydrochloride;Drug: Fluorouracil<br>* 500 mg/m², D1 and every 3 weeks<br>|
| Experimental: 6 DE<br>Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I | Biological: Trastuzumab<br>* 8 mg/kg at month M6, followed by a maintenance dose of 6 mg/kg every 3 weeks for a 1 year (i.e. 18 injections in total)<br>* Other names: Herceptin;Drug: docetaxel<br>* on day D1 of each cycle : dose: 75 mg/m², route: i.v. injection over 1 hour, every 3 weeks<br>Drug: Epirubicin<br>* 100 mg/m², D1 and every 3 weeks<br>* Other names: epirubicin hydrochloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 5 years from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Herceptin safety |  | 5 years from randomization | 
| Overall survival |  | 5 years from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II breast cancer, stage IIIA breast cancer