6xFU/Epirubicin/Cyclophosphamide (FEC) Compared to 3xFEC-3xDocetaxel in High-risk Node-negative Breast Cancer Patients

NCT ID: NCT01222052

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 4150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2019-02-28

Brief Summary

In low-risk node-negative breast cancer patients adjuvant chemotherapy should be spared. The identification of this subgroup can be based either on clinical and pathological or on tumour-biological criteria. Due to their high prognostic impact, the tumour-biological invasion markers uPA/PAI-1 (urokinase-type plasminogen activator and its inhibitor PAI-1) are potential candidates to effectively assess the risk of relapse in node-negative breast cancer. This study is aimed to compare the risk assessment by the traditional clinico-pathological factors and by tumour-biological factors. The second study question refers to the comparison between an adjuvant combination treatment with FE100C*6 and a sequential treatment with FE100C*3 and Docetaxel*3.

Detailed Description

1. To compare FEC*6 with FEC*3 followed by DOC*3 with regard to:

• the primary endpoint of the study: Disease-Free Survival (DFS)
• the secondary endpoints: Overall Survival (OS), compliance, and toxicity of chemotherapy in each patient group

2. To compare patients with low risk according to clinico-pathological versus those according to biological risk criteria with regard to:

• the proportion of low risk versus high risk patients
• DFS
• OS (secondary endpoint)

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A Taxane-containing

3 courses FEC q3weeks followed by 3 courses Docetaxel q3weeks

Group Type: EXPERIMENTAL

5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

Intervention Type: DRUG

Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks

Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks

Arm B standard anthracyclin

6 courses of FEC q3weeks

Group Type: ACTIVE_COMPARATOR

5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

Intervention Type: DRUG

Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks

Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks

Observation

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

5-Fluorouracil, Epirubicin, Cyclophosphamide, Docetaxel

Arm A 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q3weeks followed by Docetaxel 100 mg/m² q3weeks

Arm B 5-FU 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2 q6weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histological proven primary breast cancer
• Tumour size >0.5 cm and <5 cm (pT1b-pT2, pN0, M0)
• Axillary lymph nodes tumour free (node-negative disease)
• Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre
• Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision.
• Paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review.
• HER-2/neu determination by immunohistochemistry. Patients will be stratified to be HER-2/neu-negative or HER-2/neu-positive (HER-2/neu Score 3+, or HER-2/neu Score 2+ and FISH positive).
• No distant metastasis
• Age >18 years, <70 years
• Performance status ECOG <2 (WHO Performance Status 0-1)
• Adequate cardiac function (echocardiographically measured left ventricular ejection fraction (LVEF) or shortening fraction (SF) within the normal limits, i.e. ≥55%)
• Adequate bone function (neutrophil count >1.5 x109 /l and platelet count >100 x109 /l)
• Adequate renal function (serum creatinine <120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin <1 x UNL, ASAT or ALAT (SGOT or SGPT) <2,5 x UNL)
• Before patient registration/randomization, written informed consent must be obtained according to ICH/EU GCP, and national/local regulations

Exclusion Criteria

• Chemotherapy contraindicated
• Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node.
• Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel
• Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
• Estimated life-expectancy <10 years (irrespective of breast cancer diagnosis)
• Patient not accessible for treatment and follow up
• Endocrine treatment not according to the latest standard recommendations of the AGO Kommission "Mamma"
• Pregnancy, lactation (sufficient non-hormonal contraception in fertile women required)
• Surgery more than six weeks ago at the start of chemotherapy
• Pre-existing polyneuropathy
• Previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix
• Prior chemotherapy or radiotherapy or endocrine therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GBG Forschungs GmbH

OTHER

Sponsor Role: collaborator

Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role: lead

Responsible Party

Christoph Thomssen

Prof. Dr. Christoph Thomssen

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christoph Thomssen, MD

Role: PRINCIPAL_INVESTIGATOR

Dpt. Gynecology University Halle Germany

Nadia Harbeck, MD

Role: PRINCIPAL_INVESTIGATOR

Breast Center University Cologne

Locations

GBG Forschungs GmbH

Neu-Isenburg, , Germany

Countries

Germany

References

Kantelhardt EJ, Vetter M, Schmidt M, Veyret C, Augustin D, Hanf V, Meisner C, Paepke D, Schmitt M, Sweep F, von Minckwitz G, Martin PM, Jaenicke F, Thomssen C, Harbeck N. Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6xFEC versus 3xFEC/3xDocetaxel. BMC Cancer. 2011 Apr 16;11:140. doi: 10.1186/1471-2407-11-140.

Reference Type: DERIVED

PMID: 21496284 (View on PubMed)

Other Identifiers

GBG 42

Identifier Type: -

Identifier Source: org_study_id

NCT02681003

Identifier Type: -

Identifier Source: nct_alias