Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as Well as Life Style Intervention

Study Overview
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Brief Summary
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This is an open-label, multicenter, 2x2 factorial design, randomized controlled, Phase III study comparing the disease free survival after randomisation in patients treated with 3 cycles of Epirubicine-Fluorouracil-Cyclophosphamide(FEC)-chemotherapy, followed by 3 cycles of Docetaxel(D)-chemotherapy, versus 6 cycles of Docetaxel- Cyclophosphamide (DC)-chemotherapy, and to compare the disease free survival in patients with BMI of 24 - 40 kg/m² after randomisation with versus without the lifestyle intervention. Patients will be required to have histopathological proof of a HER2/neu negative tumor and: axillary lymph node metastases (pN1-3) or high risk node negative, defined as: 'pT ≥2 or histopathological grade 3, or age ≤35 or negative hormone receptor status, but are not allowed to have evidence of distant disease. Patients will have to be entered into the study no later than 6 weeks after complete resection of the primary tumor. No other antineoplastic treatment other than surgical treatment, the defined cytotoxic and endocrine treatment and radiotherapy will be allowed prior to study entry and during the course of the study.

Detailed Description
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Rationale: Taxane based chemotherapy will be established as treatment standard in the adjuvant setting of early breast cancer 3xFEC100, followed by 3xDoc100 has been established as standard treatment option for node-positive breast cancer Anthracycline based regimens do not seem to be superior in Her2/neu-negative patients (Gennari et al., Slamon et al.) Dietary intervention can improve outcome in patients with early breast cancer (WINS, Chlebowski et al.) Primary Endpoints: The first primary objective of this study is to compare disease free survival after randomisation in patients treated with a combination of 5-FU/Epirubicine/Cyclophosphamide followed by Docetaxel vs. Docetaxel/Cyclophosphamide The second primary objective of this study is to compare disease free survival after randomisation in patients with vs. without lifestyle intervention Design: Prospectively randomized open label Phase III study with 2x2 factorial design

Official Title
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Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as Well as Life Style Intervention Strategies

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Drug-based intervention
* Behavioral: Lifestyle-based Intervention


Participation Criteria
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Eligibility Criteria
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Patients may be included in the study only if they meet all the following criteria: Primary epithelial invasive carcinoma of the breast pT1-4, pN0-3, pM0 No evidence of HER2/neu overexpressing (IHC neg or +) or amplifying (FISH neg.) tumor Histopathological proof of axillary lymph node metastases (pN1-3) or high risk node negative, defined as at least one criterion of the following: 'pT ≥2, histopathological grade 3, age ≤35, negative hormone receptor' Complete resection of the primary tumor with margins of resection free of invasive carcinoma not more than 6 weeks ago Females ≥ 18 years of age Performance status ≤ 2 on ECOG-Scale Adequate bone marrow reserve: leucocytes ≥ 3.0 x 109/l and platelets ≥ 100 x 109/l Bilirubin within the reference laboratory's normal range, ASAT (SGOT), ALAT (SGPT) and AP within 1,5 fold of the reference laboratory's normal range for patients Willingness to participate in a telephone-based lifestyle intervention programme [10.] Intention of regular follow up visits for the duration of the study [11.] Ability to understand the nature of the study and to give written informed consent Patients will be excluded from the study for any of the following reasons: Inflammatory breast cancer Previous or concomitant cytotoxic or other systemic antineoplastic treatment which is not part of this study A second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) Cardiomyopathy with impaired ventricular function (NYHA > II), cardiac arrhythmias influencing LVEF and requiring medication, history of myocardial infarction or angina pectoris within the last 6 months, or arterial hypertension not being controlled by medication Any known hypersensitivity against Docetaxel, Epirubicine, Cyclophosphamide, or any other medication included in the study protocol. The contraindication, warning notices and measures of precaution of the products, as notified in the product infroamtion, have to be respected Use of any investigational agent within 3 weeks prior to inclusion Patients in pregnancy or breast feeding (in premenopausal women anticonception has to be assured) Insulin-requiring diabetes mellitus (non-insulin requiring patients with type 2 diabetes are eligible for the study) Serious digestive and/or absorptive problems that exclude adherence to the study diet [10.] Self-reported inability to walk at least one kilometer (at any pace) [11.] Cardiovascular, respiratory or musculoskeletal disease or joint problems that preclude moderate physical activity. Moderate arthritis that does not preclude physical activity is not a reason for exclusion [12.] Psychiatric disorders or conditions that would preclude participation in the study intervention [13.] Patients not sufficiently fluent in German language to understand the nature of this study and any of the interventional measures

Ages Eligible for Study
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Minimum Age: 18 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: AA<br>Drug intervention | Drug: Drug-based intervention<br>* Randomization A AA: 3 cycles of 5-Fluorouracil 500 mg/m² i.v. body surface area and Epirubicine 100 mg/m² i.v. and Cyclophosphamide 500 mg/m² i.v., (FEC100), each administered on day 1, repeated on day 22, subsequently followed by 3 cycles of Docetaxel 100 mg/m² body surface area i.v. (D), administered on day 1, repeated on day 22 AB: 6 cycles of Docetaxel 75 mg/m² and Cyclophosphamide 600 mg/m² i.v. body surface area i.v. (DC), administered on day 1, repeated on day 22<br>|
| Active Comparator: BA<br>Lifestyle intervention | Behavioral: Lifestyle-based Intervention<br>* All Patients with a Body Mass Index (BMI) of 24 - 40 kg/m² at the time of enrollment will be subsequently randomized as follows: Second randomization B BA: Lifestyle intervention program to reduce body weight comprising individual weight loss, diet and physical activity goals in the framework of a 2-year standardized and structured telephone and mail-based intervention.<br>|
| No Intervention: BB<br>No individualized lifestyle intervention program. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The first primary objective of this study is to compare disease free survival after randomisation in patients treated with a combination of 5-FU/Epirubicine/Cyclophosphamide followed by Docetaxel vs. Docetaxel/Cyclophosphamide |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The second primary objective of this study is to compare disease free survival after randomisation in patients with vs. without lifestyle intervention |  | 60 months |