EC Followed Docetaxel Versus ET Followed Capecitabine as Adjuvant Chemotherapy for Node Positive Operable Breast Cancer

NCT00129935 | Completed Phase 3 Results

• 1 other identifier: GEICAM 2003-10
• Study Type: interventional
• Target: 1,384
• Locations: 1 country
• Sites: 58

Brief Summary

This is a prospective, randomised phase III trial, to compare the efficacy and safety profiles of two types of adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2) negative, node positive breast cancer patients. Control Arm: This includes 4 cycles of EC 90/600 mg/m2 day 1 every 3 weeks, followed by 4 cycles of T 100 mg/m2 day 1 every 3 weeks. Experimental Arm: This includes 4 cycles of ET 90/75 mg/m2, day 1 every 3 weeks, followed by 4 cycles of capecitabine 1250 mg/m2, twice a day, via oral intake, for 14 days, and then a one-week rest period. Premenopausal women with hormone receptor positive tumours must receive 5 years of tamoxifen after the end of chemotherapy. Postmenopausal women with hormone receptor positive tumours can receive tamoxifen or aromatase inhibitors (or both) after the end of chemotherapy. Patients may receive radiotherapy when clinically indicated.

Conditions

Breast Cancer

Keywords

HER2 negative breast cancer; Node positive breast cancer; Adjuvant treatment; Oral chemotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Disease-free Survival (DFS) Event

  A participant was considered to have had a DFS event if there was evidence of local, regional or metastatic recurrence, second primary cancer (with the exception of carcinoma of squamous cells or basal cells of the skin, cervical carcinoma in situ or lobular or ductal carcinoma in situ of the breast) or death for any reason.

  5 years

Secondary Outcomes (5)

• Number of Participants With Overall Survival (OS) Event

  Up to 5 years

• The Number of Participants Who Experienced Adverse Events (AE)

  5 years

• Quality of Life Questionnaire: Number of Participants With Hair Loss

  Up to 24 months

• Quality of Life Questionnaire: Number of Participants With Hair Loss Recovery

  Up to 30 months

• Quality of Life Questionnaire: Time to Taking Off the Wig

  Up to 30 months

Study Arms (2)

Arm A: EC-T

ACTIVE COMPARATOR

Epirubicin with cyclophosphamide, followed by docetaxel (EC-T): Epirubicin 90 mg/ m2 in combination with cyclophosphamide 600 mg/m2 (EC) every 21 days for 4 cycles, followed by docetaxel 100 mg/m2 (T) every 21 days for 4 cycles.

Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Arm B: ET-X

EXPERIMENTAL

Epirubicin and docetaxel followed by capecitabine (ET-X):Epirubicin 90 mg/m2 and docetaxel 75 mg/ m2 (ET) every 21 days for 4 cycles, followed by capecitabine 1,250 mg/m2 bid for 14 days, followed by a 7-day rest for 4 cycles.

Drug: Docetaxel; Drug: Capecitabine; Drug: Epirubicin

Interventions

Docetaxel DRUG

Also known as: Taxotere

Arm A: EC-T; Arm B: ET-X

Capecitabine DRUG

Also known as: Xeloda

Arm B: ET-X

Epirubicin DRUG

Also known as: Ellence

Arm A: EC-T; Arm B: ET-X

Cyclophosphamide DRUG

Also known as: cytoxan

Arm A: EC-T

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 operable invasive adenocarcinoma of the breast (T1-T3). Tumours must be HER2 negative. Time window between surgery and study randomization must be less than 60 days.
• Surgery must consist of mastectomy or conservative surgery with axillary lymph node dissection. Margins free of disease and ductal carcinomas in situ (DCIS) are required. Lobular carcinoma is not considered a positive margin.
• Positive axillary lymph nodes defined as at least 1 out of 10 nodes with presence of disease. If sentinel node technique is used, sentinel node can be the only node affected. Patients belonging to the following classifications are eligible: TNM pathologic stage N1a, TNM pathologic stage N2a, TNM pathologic stage N3a.
• Status of hormone receptors in primary tumour. Results must be available before the end of adjuvant chemotherapy.
• Patients must not present evidence of metastatic disease. Status of HER2 in primary tumour, known before randomization. Patients with immune histochemistry (IHC) 0 or +1 are eligible. For patients with IHC 2+, fluorescence in situ hybridization (FISH) is mandatory and result must be negative.
• Age \>= 18 and \<= 70 years old.
• Performance status (Karnofsky index) \>= 80.
• Normal electrocardiogram (EKG) in the 12 weeks prior to randomization. If needed, normal cardiac function must be confirmed by left ventricular ejection fraction (LVEF).
• Laboratory results (within 14 days prior to randomization):
• Hematology: neutrophils \>= 1.5 x 10\^9/l; platelets \>= 100 x 10\^9/l; hemoglobin \>= 10 mg/dl;
• Hepatic function: total bilirubin \<= 1 upper normal limit (UNL); serum glutamic-oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT) \<= 2.5 UNL; alkaline phosphatase \<= 2.5 UNL. If values of SGOT and SGPT \> 1.5 UNL are associated to alkaline phosphatase \> 2.5 UNL, patient is not eligible;
• Renal function: creatinine \<= 175 mmol/l (2 mg/dl); creatinine clearance \>= 60 ml/min;
• Pharmacogenetics: one blood sample is needed for single nucleotide polymorphism (SNP) assessment.
• Complete stage workup during the 12 weeks prior to randomization (mammograms are allowed within a 20 week window). All patients must have a bilateral mammogram, thorax x-ray, abdominal echography and/or computed tomography (CT)-scan. If bone pain, and/or alkaline phosphatase elevation, a bone scintigraphy is mandatory. This test is recommended for all patients. Other tests: as clinically indicated.

You may not qualify if:

• Prior systemic therapy for breast cancer.
• Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy.
• Prior radiotherapy for breast cancer.
• Bilateral invasive breast cancer.
• Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments.
• Any T4 or M1 tumour.
• Axillary lymph nodes: patients belonging to the following classifications are excluded: TNM pathologic stage N1b, TNM pathologic stage N1c, TNM pathologic stage N2b, TNM pathologic stage N3b, TNM pathologic stage N3c.
• HER2 positive breast cancer (IHC 3+ or positive FISH result).
• Pre-existing grade \>= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria version 2.0 \[NCICTC v-2.0\]).
• Any other serious medical pathology, such as congestive heart failure; unstable angina; history of myocardial infarction during the previous year; uncontrolled hypertension or high risk arrhythmias.
• History of neurological or psychiatric disorders, which could preclude the patients from free informed consent.
• Active uncontrolled infection.
• Active peptic ulcer; unstable diabetes mellitus.
• Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumour curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
• Chronic treatment with corticosteroids.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Sanofi: collaborator
• Hoffmann-La Roche: collaborator
• Pfizer: collaborator

Study Sites (58)

Hospital Arquitecto Marcide

Ferrol, A Coruña, 15405, 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 Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital del Espíritu Santo

Santa Coloma de Gramenet, Barcelona, 08923, Spain

Location

Hospital Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Hospital General Universitario de Vic

Vic, Barcelona, 08500, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Provincial de Castellón

Castellon, Castellón, 12002, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Cordoba, 14004, Spain

Location

Hospital de Jerez de la Frontera

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Onkologikoa

Donostia / San Sebastian, Guipúzcoa, 20012, Spain

Location

Hosptial Donostia

Donostia / San Sebastian, Guipúzcoa, 20014, Spain

Location

Hospital de Barbastro

Barbastro, Huesca, 22300, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Hospital Universitario Severo Ochoa

Leganés, Madrid, 28911, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario San Joan de Reus

Reus, Tarragona, 43201, 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 Albacete

Albacete, 02066, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Universitario Virgen de los Lirios

Alicante, 03804, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, 11009, Spain

Location

Instituto Catalán de Oncología de Girona

Girona, 17007, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital General Universitario de Guadalajara

Guadalajara, 19002, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28021, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Clínico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital Clínico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, 30008, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Complejo Hospitalario Unviersitario de Ourense

Ourense, 32005, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario de Valme

Seville, 41014, 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

Hospial General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Universitario Arnau de Vilanova de Valencia

Valencia, 46015, Spain

Location

Hospital Provincial Rodríguez Chamorro 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

Related Publications (4)

• Martin M, Ruiz Simon A, Ruiz Borrego M, Ribelles N, Rodriguez-Lescure A, Munoz-Mateu M, Gonzalez S, Margeli Vila M, Barnadas A, Ramos M, Del Barco Berron S, Jara C, Calvo L, Martinez-Janez N, Mendiola Fernandez C, Rodriguez CA, Martinez de Duenas E, Andres R, Plazaola A, de la Haba-Rodriguez J, Lopez-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sanchez-Rovira P, Baena-Canada JM, Casas M, del Carmen Camara M, Carrasco EM, Lluch A. Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study. J Clin Oncol. 2015 Nov 10;33(32):3788-95. doi: 10.1200/JCO.2015.61.9510. Epub 2015 Sep 28.

  PMID: 26416999 RESULT

• van Mackelenbergh MT, Seither F, Mobus V, O'Shaughnessy J, Martin M, Joensuu H, Untch M, Nitz U, Steger GG, Miralles JJ, Barrios CH, Toi M, Bear HD, Muss H, Reimer T, Nekljudova V, Loibl S. Effects of capecitabine as part of neo-/adjuvant chemotherapy - A meta-analysis of individual breast cancer patient data from 13 randomised trials including 15,993 patients. Eur J Cancer. 2022 May;166:185-201. doi: 10.1016/j.ejca.2022.02.003. Epub 2022 Mar 16.

  PMID: 35305453 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

• Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

  PMID: 34037241 DERIVED

Related Links

• Click here for more information about this study: GEICAM 2003-10

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; Capecitabine; 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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; 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

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group

geicam@geicam.org

+34916592870

Study Officials

• Study Director

  Hospital Clínico Universitario San Carlos

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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 11, 2005
• First Posted: August 12, 2005
• Study Start: February 1, 2004
• Primary Completion: June 1, 2013
• Study Completion: April 4, 2019
• Last Updated: March 31, 2023
• Results First Posted: October 25, 2019

Record last verified: 2023-03

Locations

ES (58)