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

NCT00129922 | Completed Phase 3

• 1 other identifier: GEICAM 9906
• Study Type: interventional
• Target: 1,289
• Locations: 1 country
• Sites: 64

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.

Conditions

Breast Cancer

Keywords

Axillary node positive breast cancer.; Sequential drug administration.; Weekly paclitaxel.

Outcome Measures

Primary Outcomes (1)

• disease-free survival

  From the date of randomization of each patient included to the 1st documented evidence of recurrence

  5 years

Secondary Outcomes (1)

• Overall survival

  From date of randomization until the date of death from any cause, assessed up to 100 months

Study Arms (2)

Fluorouracil+Epirubicin+Cyclophosphamide

ACTIVE COMPARATOR

5-FU+4-Epirubicin+Cyclophosphamide

Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

FEC followed by Paclitaxel

EXPERIMENTAL

5-FU+4-Epirubicin+Cyclophosphamide

Drug: paclitaxel; Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

paclitaxel DRUG

Also known as: Taxol

FEC followed by Paclitaxel

Fluorouracil DRUG

Also known as: 5-FU

FEC followed by Paclitaxel; Fluorouracil+Epirubicin+Cyclophosphamide

Epirubicin DRUG

Also known as: 4-Epirubicin

FEC followed by Paclitaxel; Fluorouracil+Epirubicin+Cyclophosphamide

Cyclophosphamide DRUG

FEC followed by Paclitaxel; Fluorouracil+Epirubicin+Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Bristol-Myers Squibb: collaborator
• Pfizer: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (64)

Hospital Universitario Virgen de los Lirios

Alcoy, Alicante, 03804, Spain

Location

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

Hospital General Universitario de Elda

Elda, Alicante, 03600, Spain

Location

Hospital Municipal de Badalona

Badalona, Barcelona, 08911, Spain

Location

Hospital Unviersitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Althaia-Xarxa Assistencial de Manresa

Manresa, Barcelona, 08240, Spain

Location

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Espíritu Santo

Santa Coloma de Gramenet, Barcelona, 08923, Spain

Location

Hospital Universitario Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital de Jerez de la Frontera

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Hospital Universitario Puerto Real

Puerto Real, Cádiz, 11510, Spain

Location

Onkologikoa

Donostia / San Sebastian, Gupúzcoa, 20012, Spain

Location

Hospital Donostia

Donostia / San Sebastian, Gupúzcoa, 20014, Spain

Location

Hospital de Barbastro

Barbastro, Huesca, 22300, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Las Palmas, 35010, Spain

Location

Complejo Hospitalario Universitario Insular-Materno Infantil

Las Palmas de Gran Canaria, Las Palmas, 35016, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario de Móstoles

Móstoles, Madrid, 28935, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital de Cabueñes

Gijón, Principality of Asturias, 33394, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital Universitario San Joan de Reus

Reus, Tarragona, 43204, Spain

Location

Hospital de la Ribera

Alzira, Valencia, 46600, Spain

Location

Hospital de Sagunto

Sagunto, Valencia, 46520, Spain

Location

Hospital Universitario Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Centro Oncológico de Galicia

A Coruña, 15009, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Clínica Oncológica Corachán

Barcelona, 08017, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, 11009, Spain

Location

Hospital General Universitario de Ciudad Real

Ciudad Real, 13005, Spain

Location

Hospital Provincial de Córdoba

Córdoba, 14004, Spain

Location

Hospital General Universitario de Guadalajara

Guadalajara, 19002, Spain

Location

Hospital Juan Ramón Jiménez

Huelva, 21005, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital de León

León, 24071, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27004, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital Clínico Unviersitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Complejo Hospitalario de Ourense

Ourense, 32005, Spain

Location

Hospital Rio Carrión

Palencia, 34005, Spain

Location

Hospital Unviersitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Virgen de la Salud

Toledo, 45005, Spain

Location

Hospital Provincial de Toledo

Toledo, 45006, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Universitario Arnau de Vilanova de Valencia

Valencia, 46015, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, 47003, Spain

Location

Hospital Provincial de Zamora

Zamora, 49021, Spain

Location

Hospital Clínico Universitario de Zaragoza "Lozano Blesa"

Zaragoza, 50009, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Hospital de Txagorritxu

Vitoria-Gasteiz, Álava, 01009, Spain

Location

Related Publications (15)

• 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 predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer. Breast Cancer Res Treat. 2010 Aug;123(1):149-57. doi: 10.1007/s10549-009-0663-z.

  PMID: 20037779 RESULT

• 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 cancer treatment plans. J Clin Bioinforma. 2011 Dec 23;1:37. doi: 10.1186/2043-9113-1-37.

  PMID: 22196354 RESULT

• 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. doi: 10.1007/s10549-010-1136-0. Epub 2010 Aug 28.

  PMID: 20803065 RESULT

• 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, Anton A, Carrasco E, Caballero R, Ellis MJ, Nielsen TO, Perou CM, Astill M, Bernard PS, Martin M. PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers. BMC Med Genomics. 2012 Oct 4;5:44. doi: 10.1186/1755-8794-5-44.

  PMID: 23035882 RESULT

• 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 breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis. Breast Cancer Res. 2013 Nov 6;15(6):R105. doi: 10.1186/bcr3572.

  PMID: 24192331 RESULT

• 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, Stijleman IJ, Tuck DP, Carrasco E, Perou CM, Bernard PS. PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer. Breast Cancer Res Treat. 2013 Apr;138(2):457-66. doi: 10.1007/s10549-013-2416-2. Epub 2013 Feb 20.

  PMID: 23423445 RESULT

• 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 Clin Oncol. 2013 Jan 10;31(2):203-9. doi: 10.1200/JCO.2012.43.4134. Epub 2012 Dec 10.

  PMID: 23233704 RESULT

• 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 node-positive, chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM 9906 trial. Breast Cancer Res. 2014 Apr 12;16(2):R38. doi: 10.1186/bcr3642.

  PMID: 24725534 RESULT

• 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, Carey LA. Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist. 2015 May;20(5):474-82. doi: 10.1634/theoncologist.2014-0372. Epub 2015 Apr 23.

  PMID: 25908555 RESULT

• 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 research-based versions of the PAM50 risk of recurrence (ROR) scores in node-positive, estrogen receptor-positive, and HER2-negative breast cancer. A GEICAM/9906 sub-study. Breast Cancer Res Treat. 2016 Feb;156(1):81-9. doi: 10.1007/s10549-016-3725-z. Epub 2016 Feb 24.

  PMID: 26909792 RESULT

• 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 Study Investigators. Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy. Clin Transl Oncol. 2018 Dec;20(12):1548-1556. doi: 10.1007/s12094-018-1885-5. Epub 2018 May 15.

  PMID: 29766456 RESULT

• 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 who received adjuvant endocrine therapy plus chemotherapy or endocrine therapy alone. Breast Cancer Res Treat. 2019 Jul;176(2):377-386. doi: 10.1007/s10549-019-05226-8. Epub 2019 Apr 30.

  PMID: 31041683 RESULT

• 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 cancer. Breast Cancer Res Treat. 2019 May;175(1):129-139. doi: 10.1007/s10549-018-05097-5. Epub 2019 Jan 23.

  PMID: 30673970 RESULT

• 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 versus double hormone receptor-positive breast cancer. A GEICAM/9906 sub-study. Eur J Cancer. 2018 May;94:199-205. doi: 10.1016/j.ejca.2018.02.018. Epub 2018 Mar 21.

  PMID: 29573665 RESULT

• Martin M, Carrasco E, Rodriguez-Lescure A, Andres R, Servitja S, Anton A, Ruiz-Borrego M, Bermejo B, Guerrero A, Ramos M, Santaballa A, Munoz M, Cruz J, Lopez-Tarruella S, Chacon JI, Alvarez I, Martinez P, Miralles JJ, Polonio O, Jara C, Aguiar-Bujanda D. Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Alamo IV registry. Breast Cancer Res Treat. 2023 Sep;201(2):151-159. doi: 10.1007/s10549-023-07002-1. Epub 2023 Jun 20.

  PMID: 37338729 DERIVED

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Fluorouracil; Epirubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Study Director

  Hospital General Universitario de Elche

  STUDY DIRECTOR

• Study Director

  Hospital Universitario Marqués de Valdecilla

  STUDY DIRECTOR

• Study Director

  Hospital Provincial de Córdoba

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2005
• First Posted: August 12, 2005
• Study Start: November 1, 1999
• Primary Completion: December 1, 2005
• Study Completion: December 1, 2007
• Last Updated: March 6, 2023

Record last verified: 2023-03

Locations

ES (64)