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

Breast Cancer Clinical Trial

— NNBC3-Europe  

Official title:

Randomized Multicenter Study Comparing 6xFEC With 3xFEC-3xDoc in High-risk Node-negative Patients With Operable Breast Cancer: Comparison of Efficacy and Evaluation of Clinico-pathological and Biochemical Markers as Risk Selection Criteria

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01222052
• Other study ID #: GBG 42
• Status: Active, not recruiting
• Phase: Phase 3
• First received: October 15, 2010
• Last updated: June 23, 2017
• Start date: January 2002
• Est. completion date: February 2019

Study information

• Verified date: June 2017
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Other known NCT identifiers

• NCT02681003

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 4150
• Est. completion date: February 2019
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Germany	GBG Forschungs GmbH	Neu-Isenburg

Sponsors (2)

Lead Sponsor	Collaborator
Martin-Luther-Universität Halle-Wittenberg	German Breast Group

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-Free Survival		after 10 years follow up
Secondary	Overall Survival		after 10 years follow up