Clinical trial NCT00129922: Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer
Official title: Phase III Study to Compare 6 Courses of FEC (Fluorouracil, Epirubicin and Cyclophosphamide) vs. 4 Courses of FEC Followed by 8 Weekly Paclitaxel Administrations, as Adjuvant Treatment for Node Positive Operable BC Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Axillary node positive breast cancer.
Sequential drug administration.
Weekly paclitaxel.
Lead sponsor: Spanish Breast Cancer Research Group
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Pfizer
name: Hoffmann-La Roche
First posted: 2005-08-12
Enrollment: 1289
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: disease-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 100 months
Other outcomes:
Locations:
city: Alcoy
country: Spain
facility: Hospital Universitario Virgen de los Lirios
state: Alicante
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Elda
country: Spain
facility: Hospital General Universitario de Elda
state: Alicante
city: Gijón
country: Spain
facility: Hospital de Cabueñes
state: Asturias
city: Badalona
country: Spain
facility: Hospital Municipal de Badalona
state: Barcelona
city: Badalona
country: Spain
facility: Hospital Unviersitario Germans Trias i Pujol
state: Barcelona
city: Manresa
country: Spain
facility: Althaia-Xarxa Assistencial de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
state: Barcelona
city: Santa Coloma De Gramenet
country: Spain
facility: Hospital Espíritu Santo
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Universitario Mutua de Terrassa
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Jerez De La Frontera
country: Spain
facility: Hospital de Jerez de la Frontera
state: Cádiz
city: Puerto Real
country: Spain
facility: Hospital Universitario Puerto Real
state: Cádiz
city: Donostia-San Sebastian
country: Spain
facility: Hospital Donostia
state: Gupúzcoa
city: Donostia-San Sebastián
country: Spain
facility: Onkologikoa
state: Gupúzcoa
city: Barbastro
country: Spain
facility: Hospital de Barbastro
state: Huesca
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr. Negrín
state: Las Palmas
city: Las Palmas De Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular-Materno Infantil
state: Las Palmas
city: Alcorcón
country: Spain
facility: Hospital Universitario Fundación Alcorcón
state: Madrid
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrid
city: Móstoles
country: Spain
facility: Hospital Universitario de Móstoles
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de la Arrixaca
state: Murcia
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Santa Cruz De Tenerife
city: Reus
country: Spain
facility: Hospital Universitario San Joan de Reus
state: Tarragona
city: Alcira
country: Spain
facility: Hospital de la Ribera
state: Valencia
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Valencia
city: Baracaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: A Coruña
country: Spain
facility: Centro Oncológico de Galicia
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Clínica Oncológica Corachán
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Ciudad Real
country: Spain
facility: Hospital General Universitario de Ciudad Real
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Provincial de Córdoba
city: Guadalajara
country: Spain
facility: Hospital General Universitario de Guadalajara
city: Huelva
country: Spain
facility: Hospital Juan Ramón Jiménez
city: Jaén
country: Spain
facility: Complejo Hospitalario de Jaén
city: León
country: Spain
facility: Hospital de León
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Málaga
country: Spain
facility: Hospital Clínico Unviersitario Virgen de la Victoria
city: Ourense
country: Spain
facility: Complejo Hospitalario de Ourense
city: Palencia
country: Spain
facility: Hospital Rio Carrión
city: Salamanca
country: Spain
facility: Hospital Unviersitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Toledo
country: Spain
facility: Hospital Provincial de Toledo
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Arnau de Vilanova de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valladolid
country: Spain
facility: Hospital Clínico Universitario de Valladolid
city: Zamora
country: Spain
facility: Hospital Provincial de Zamora
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario de Zaragoza "Lozano Blesa"
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Vitoria-Gasteiz
country: Spain
facility: Hospital de Txagorritxu
state: Álava
Study officials:
affiliation: Hospital General Universitario de Elche
name: Study Director
role: STUDY_DIRECTOR
affiliation: Hospital Universitario Marqués de Valdecilla
name: Study Director
role: STUDY_DIRECTOR
affiliation: Hospital Provincial de Córdoba
name: Study Director
role: STUDY_DIRECTOR
References:
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