Docetaxel, Doxorubicin (A), Cyclophosphamide (C) (TAC) vs 5-Fluorouracil, A, C (5FAC) Breast Cancer Adjuvant Treatment

Study Overview
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Brief Summary
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This is a prospective, non-blinded randomized phase III trial. Patients will be post-surgically stratified at inclusion first according to the participating institution, then according to menopausal status and will be randomly assigned to receive either: TAC: Docetaxel 75 mg/m2 as a 1 hour intravenous (i.v.) infusion on day 1 every 3 weeks (q3w) in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks. FAC: 5-fluorouracil 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks in combination with doxorubicin 50 mg/m2 as an i.v. bolus and cyclophosphamide 500 mg/m2 as an i.v. bolus on day 1 every 3 weeks.

Detailed Description
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Primary objective: To compare disease-free survival (DFS) after treatment with docetaxel in combination with doxorubicin and cyclophosphamide (TAC) to 5-Fluorouracil in combination with doxorubicin and cyclophosphamide (FAC) as adjuvant treatment of high risk operable breast cancer patients with negative axillary lymph nodes. Secondary objectives: To compare overall survival (OS) between the 2 above mentioned arms. To compare toxicity and quality of life between the 2 above mentioned arms. To evaluate pathologic markers for predicting efficacy (hormonal receptors and human epidermal growth factor receptor 2 (HER2) protein expression).

Official Title
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Phase III Randomized Comparing Docetaxel, Doxorubicin and Cyclophosphamide (TAC) vs 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of High Risk Operable Breast Cancer Patients With Negative Axillary Lymph Nodes

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Docetaxel
* Drug: 5-fluorouracil
* Drug: Doxorubicin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10 axillary nodes dissection) and high risk criteria according to St. Gallen consensus criteria. Histologically proven breast cancer. Interval between surgery and registration is less than 60 days. Definitive surgical treatment must be either mastectomy, or breast conservative surgery. Margins of resected specimen from surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ is not considered as positive margin. Patients without proven metastatic disease. Estrogen and progesterone receptors performed on the primary tumour prior to randomization. Age between 18 years and 70 years. Karnofsky performance status index > 80 %. Adequate hepatic, renal and heart functions. Adequate hematology levels. Negative pregnancy test Exclusion Criteria: Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy). Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy. Prior radiation therapy for breast cancer. Bilateral invasive breast cancer. Pregnant, or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment . Any T4 or N1-3 or M1 breast cancer. Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria. Other serious illness or medical condition Past or current history of neoplasm other than breast carcinoma. Ipsilateral ductal carcinoma in-situ (DCIS) of the breast. Lobular carcinoma in-situ (LCIS) of the breast. Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped before study entry. Definite contraindications for the use of corticosteroids. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry. Concurrent treatment with any other anti-cancer therapy. Male patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Arm A: FAC<br>FAC (5-fluorouracil, doxorubicin, cyclophosphamide): 5-fluorouracil 500 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv | Drug: 5-fluorouracil<br> <br> * Other names: Adrucil;Drug: Doxorubicin<br> <br> * Other names: adriamycin;Drug: Cyclophosphamide<br> <br> * Other names: cytoxan;|
| Experimental: Arm B: TAC<br>TAC (docetaxel, doxorubicin, cyclophosphamide): Docetaxel 75 mg/m2 iv on day 1, each 3 weeks, in combination with doxorubicin 50 mg/m2 iv and cyclophosphamide 500 mg/m2 iv | Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Doxorubicin<br> <br> * Other names: adriamycin;Drug: Cyclophosphamide<br> <br> * Other names: cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS) Events | DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death. | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS was determined from the date of randomization until the date of death for any reason. OS is calculated from the date of randomization up to the first date of death by any cause. | 10 years | 
| The Number of Participants Who Experienced Adverse Events (AE) | Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0. | Through study treatment, and average of 4 months | 
| Best Score During Study for Global Health Status Scale | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used. Questionnaires were self-administered to patients during the 14 days prior to randomisation baseline, at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study. The Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL. | 120 weeks | 
| Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup | Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first. | 10 year | 
| Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup | Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first. | 10 year | 
| Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup | Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. | 10 year | 
| Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup | Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first. | 10 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High risk node negative breast cancer, Disease-Free survival, Quality of life