Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Fluorouracil; Drug: paclitaxel; Drug: Epirubicin; Drug: Cyclophosphamide

• Registration Number: NCT00129922
• Lead Sponsor: Spanish Breast Cancer Research Group

Brief Summary

The efficacy of adjuvant chemotherapy is limited in patients with a high risk of recurrence.

Also, for axillary positive node patients, optimum chemotherapy regimens are still under discussion. Some previous studies suggest that, in the subset of node-positive patients, treatments based on sequential administration of anthracyclines and taxanes are more efficient. Paclitaxel dose-dense (weekly) administration renders an improved therapeutic index (activity/toxicity).

The study is designed to compare 6 courses of FEC scheme (600/90/600), a combination of proven efficacy in node positive breast cancer patients, versus 4 FEC courses followed by 8 weekly paclitaxel administrations (100mg/m2).

The study hypothesis is that 5-year disease-free survival in the control arm will be 60%. The investigators expect to increase this by 8% with the experimental treatment. With an alpha error of 0.05, 80% power, and a post-randomization estimated drop-out rate of 10%, 1250 patients are needed, 625 per arm.

Detailed Description

The primary endpoint of study-5-year disease-free survival (DFS) will be assessed by Kaplan Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular markers. Associations and interactions will be assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests will be two-sided.

Study Timeline

• Study Start: 1999-11
• Study First Submitted: 2005-08-10
• Study First Submitted QC: 2005-08-11
• Study First Posted: 2005-08-12
• Primary Completion: 2005-12
• Study Completion: 2007-12
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-03
• Last Update Posted: 2023-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 1289

Inclusion Criteria

• Written informed consent.
• Histological diagnosis of breast cancer.
• Node positive operable breast cancer (stages II-III).
• Breast cancer surgery, consisting of radical mastectomy or conservative surgery, plus lymphadenectomy with at least 6 extirpated nodes. Surgery must have happened in the 8 weeks prior to randomisation.
• Age >=18 and <= 70 years old.
• Negative pregnancy test. Adequate contraceptive method during the study participation.
• Performance status of 90-100 (Karnofsky index) or ECOG <=1.
• Haemoglobin >= 10 g/dl; neutrophils > 1,500/cc; platelets > 100,000/cc.
• Adequate hepatic function with bilirubin, SGOT and SGPT < 1.5 x upper normal limit (UNL).
• Adequate cardiac function documented by left ventricular ejection fraction (LVEF).
• Adequate renal function with creatinine < 1.5 mg/dl.

Exclusion Criteria

• Previous chemotherapy, hormone therapy and/or radiotherapy for breast cancer.
• Bilateral breast cancer. Lobular in situ carcinoma.
• Previous or current malignancies, except for basal skin carcinoma, cervical in situ carcinoma or superficial bladder carcinoma, adequately treated.
• History of arrhythmias and/or congestive heart failure or cardiac blocking grade 2-3; history of myocardial infarction in 6 months before recruitment.
• Inability for treatment and study compliance.
• Pregnant or lactating women.
• Active infection.
• History of hypersensitivity to cremophor or cyclosporine.
• Pre-existing grade 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCI CTC]).
• Hormonal receptor status not determined.
• Any other criteria which, in investigator's opinion, may jeopardize patient's security or compliance.
• Administration of other investigational product in the 30 days prior to randomisation; current participation in another clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluorouracil+Epirubicin+Cyclophosphamide	Fluorouracil	5-FU+4-Epirubicin+Cyclophosphamide
Fluorouracil+Epirubicin+Cyclophosphamide	Epirubicin	5-FU+4-Epirubicin+Cyclophosphamide
Fluorouracil+Epirubicin+Cyclophosphamide	Cyclophosphamide	5-FU+4-Epirubicin+Cyclophosphamide
FEC followed by Paclitaxel	paclitaxel	5-FU+4-Epirubicin+Cyclophosphamide
FEC followed by Paclitaxel	Fluorouracil	5-FU+4-Epirubicin+Cyclophosphamide
FEC followed by Paclitaxel	Epirubicin	5-FU+4-Epirubicin+Cyclophosphamide
FEC followed by Paclitaxel	Cyclophosphamide	5-FU+4-Epirubicin+Cyclophosphamide

Primary Outcome Measures

Name	Time	Method
disease-free survival	5 years	From the date of randomization of each patient included to the 1st documented evidence of recurrence

Secondary Outcome Measures

Name	Time	Method
Overall survival	From date of randomization until the date of death from any cause, assessed up to 100 months	Overall survival will be measured from the day of randomization to the date of death from any cause

Trial Locations

Locations (64)

Hospital Universitario Virgen de los Lirios; 🇪🇸 Alcoy, Alicante, Spain

Hospital General Universitario de Elche; 🇪🇸 Elche, Alicante, Spain

Hospital General Universitario de Elda; 🇪🇸 Elda, Alicante, Spain

Hospital de Cabueñes; 🇪🇸 Gijón, Asturias, Spain

Hospital Municipal de Badalona; 🇪🇸 Badalona, Barcelona, Spain

Hospital Unviersitario Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Althaia-Xarxa Assistencial de Manresa; 🇪🇸 Manresa, Barcelona, Spain

Corporació Sanitaria Parc Taulí; 🇪🇸 Sabadell, Barcelona, Spain

Hospital Espíritu Santo; 🇪🇸 Santa Coloma De Gramenet, Barcelona, Spain

Hospital Universitario Mutua de Terrassa; 🇪🇸 Terrassa, Barcelona, Spain

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