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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129922
• Other study ID #: GEICAM 9906
• Status: Completed
• Phase: Phase 3
• Start date: November 1999
• Est. completion date: December 2007

Study information

• Verified date: March 2023
• Source: Spanish Breast Cancer Research Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1289
• Est. completion date: December 2007
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• paclitaxel

• Fluorouracil

• Epirubicin

• Cyclophosphamide

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital de la Ribera	Alcira	Valencia
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Universitario Virgen de los Lirios	Alcoy	Alicante
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Municipal de Badalona	Badalona	Barcelona
Spain	Hospital Unviersitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario Cruces	Baracaldo	Vizcaya
Spain	Hospital de Barbastro	Barbastro	Huesca
Spain	Clínica Oncológica Corachán	Barcelona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Puerta del Mar	Cádiz
Spain	Hospital General Universitario de Ciudad Real	Ciudad Real
Spain	Hospital Provincial de Córdoba	Córdoba
Spain	Hospital Donostia	Donostia-San Sebastian	Gupúzcoa
Spain	Onkologikoa	Donostia-San Sebastián	Gupúzcoa
Spain	Hospital Clínico Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital General Universitario de Elda	Elda	Alicante
Spain	Hospital de Cabueñes	Gijón	Asturias
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Hospital Juan Ramón Jiménez	Huelva
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital de Jerez de la Frontera	Jerez De La Frontera	Cádiz
Spain	Hospital Universitario de Canarias	La Laguna	Santa Cruz De Tenerife
Spain	Complejo Hospitalario Universitario Insular-Materno Infantil	Las Palmas De Gran Canaria	Las Palmas
Spain	Hospital Universitario de Gran Canaria Dr. Negrín	Las Palmas De Gran Canaria	Las Palmas
Spain	Hospital de León	León
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	Madrid
Spain	Hospital Clínico Unviersitario Virgen de la Victoria	Málaga
Spain	Althaia-Xarxa Assistencial de Manresa	Manresa	Barcelona
Spain	Hospital Universitario de Móstoles	Móstoles	Madrid
Spain	Hospital General Universitario Morales Meseguer	Murcia
Spain	Complejo Hospitalario de Ourense	Ourense
Spain	Hospital Rio Carrión	Palencia
Spain	Complejo Hospitalario de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Puerto Real	Puerto Real	Cádiz
Spain	Hospital Universitario San Joan de Reus	Reus	Tarragona
Spain	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Hospital de Sagunto	Sagunto	Valencia
Spain	Hospital Unviersitario de Salamanca	Salamanca
Spain	Hospital Espíritu Santo	Santa Coloma De Gramenet	Barcelona
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Provincial de Toledo	Toledo
Spain	Hospital Virgen de la Salud	Toledo
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Hospital Universitario Arnau de Vilanova de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital Clínico Universitario de Valladolid	Valladolid
Spain	Hospital de Txagorritxu	Vitoria-Gasteiz	Álava
Spain	Hospital Provincial de Zamora	Zamora
Spain	Hospital Clínico Universitario de Zaragoza "Lozano Blesa"	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (4)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Bristol-Myers Squibb, Hoffmann-La Roche, Pfizer

Country where clinical trial is conducted

Spain, 

References & Publications (14)

Bastien RR, Rodriguez-Lescure A, Ebbert MT, Prat A, Munarriz B, Rowe L, Miller P, Ruiz-Borrego M, Anderson D, Lyons B, Alvarez I, Dowell T, Wall D, Segui MA, Barley L, Boucher KM, Alba E, Pappas L, Davis CA, Aranda I, Fauron C, Stijleman IJ, Palacios J, A — View Citation

Camp NJ, Madsen MJ, Herranz J, Rodriguez-Lescure A, Ruiz A, Martin M, Bernard PS. Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast — View Citation

Cheang MC, Martin M, Nielsen TO, Prat A, Voduc D, Rodriguez-Lescure A, Ruiz A, Chia S, Shepherd L, Ruiz-Borrego M, Calvo L, Alba E, Carrasco E, Caballero R, Tu D, Pritchard KI, Levine MN, Bramwell VH, Parker J, Bernard PS, Ellis MJ, Perou CM, Di Leo A, Ca — View Citation

de la Haba-Rodriguez J, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Carrasco E, Escudero MJ, Martin M. Regional and seasonal influence in patient's toxicity to adjuvant chemotherapy for early breast cancer. Breast Cancer Res Treat. 2011 Jan;125(1):273-8 — View Citation

Ebbert MT, Bastien RR, Boucher KM, Martin M, Carrasco E, Caballero R, Stijleman IJ, Bernard PS, Facelli JC. Characterization of uncertainty in the classification of multivariate assays: application to PAM50 centroid-based genomic predictors for breast can — View Citation

Ethier JL, Ocana A, Rodriguez Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Ramos M, Gracia Marco J, Lluch A, Alvarez I, Casas M, Sanchez-Arago M, Carrasco E, Caballero R, Amir E, Martin M. Outcomes of single ve — View Citation

Martin M, Brase JC, Calvo L, Krappmann K, Ruiz-Borrego M, Fisch K, Ruiz A, Weber KE, Munarriz B, Petry C, Rodriguez CA, Kronenwett R, Crespo C, Alba E, Carrasco E, Casas M, Caballero R, Rodriguez-Lescure A. Clinical validation of the EndoPredict test in n — View Citation

Martin M, Brase JC, Ruiz A, Prat A, Kronenwett R, Calvo L, Petry C, Bernard PS, Ruiz-Borrego M, Weber KE, Rodriguez CA, Alvarez IM, Segui MA, Perou CM, Casas M, Carrasco E, Caballero R, Rodriguez-Lescure A. Prognostic ability of EndoPredict compared to re — View Citation

Martin M, Prat A, Rodriguez-Lescure A, Caballero R, Ebbert MT, Munarriz B, Ruiz-Borrego M, Bastien RR, Crespo C, Davis C, Rodriguez CA, Lopez-Vega JM, Furio V, Garcia AM, Casas M, Ellis MJ, Berry DA, Pitcher BN, Harris L, Ruiz A, Winer E, Hudis C, Stijlem — View Citation

Martin M, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Abad M, Dominguez S, Florian J, Llorca C, Mendez M, Godes M, Cubedo R, Murias A, Batista N, Garcia MJ, Caballero R, de Alava E. Molecular predict — View Citation

Pajares B, Pollan M, Martin M, Mackey JR, Lluch A, Gavila J, Vogel C, Ruiz-Borrego M, Calvo L, Pienkowski T, Rodriguez-Lescure A, Segui MA, Tredan O, Anton A, Ramos M, Camara Mdel C, Rodriguez-Martin C, Carrasco E, Alba E. Obesity and survival in operable — View Citation

Prat A, Cheang MC, Martin M, Parker JS, Carrasco E, Caballero R, Tyldesley S, Gelmon K, Bernard PS, Nielsen TO, Perou CM. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J — View Citation

Sestak I, Martin M, Dubsky P, Kronenwett R, Rojo F, Cuzick J, Filipits M, Ruiz A, Gradishar W, Soliman H, Schwartzberg L, Buus R, Hlauschek D, Rodriguez-Lescure A, Gnant M. Prediction of chemotherapy benefit by EndoPredict in patients with breast cancer w — View Citation

Templeton AJ, Rodriguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, Santaballa A, Rodriguez CA, Crespo C, Ramos M, Gracia-Marco JM, Lluch A, Alvarez I, Casas MI, Sanchez-Arago M, Caballero R, Carrasco E, Amir E, Martin M, Ocana A; GEICAM 9906 Stud — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival	From the date of randomization of each patient included to the 1st documented evidence of recurrence	5 years
Secondary	Overall survival	Overall survival will be measured from the day of randomization to the date of death from any cause	From date of randomization until the date of death from any cause, assessed up to 100 months

External Links

•   Click here for more information about this study: GEICAM 9906