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

NCT ID: NCT00129935

Last Updated: 2023-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1384 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2019-04-04

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.

Detailed Description

Estimation of the 5-year disease-free survival in the control arm is 72%. The experimental arm is expected to increase the 5-year disease-free survival by 7% (up to 79%). With an alpha error of 0.05 and 80% power, 592 patients per arm are needed. Assuming a 17% post-randomization drop-out, 691 patients per arm are needed.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: EC-T

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.

Group Type: ACTIVE_COMPARATOR

Docetaxel

Intervention Type: DRUG

Epirubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Arm B: ET-X

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Epirubicin

Intervention Type: DRUG

Interventions

Docetaxel

Intervention Type: DRUG

Capecitabine

Intervention Type: DRUG

Epirubicin

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Other Intervention Names

Taxotere; Xeloda; Ellence; cytoxan

Eligibility Criteria

Inclusion Criteria

• 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.
• Patients able to comply with treatment and study follow-up.
• Negative pregnancy test done in the 14 prior days to randomization.

Exclusion Criteria

• 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.
• Contraindications for corticosteroid administration.
• Concomitant treatment with raloxifene, tamoxifen or other selective estrogen receptor modulators (SERMs), either for osteoporosis treatment or for prevention. These treatments must stop before randomisation.
• Concomitant treatment with other investigational products; participation in other clinical trials with a non-marketed drug in the 20 previous days before randomization.
• Concomitant treatment with another therapy for cancer.
• Males.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Hospital Clínico Universitario San Carlos

Locations

Hospital Arquitecto Marcide

Ferrol, A Coruña, Spain

Hospital General Universitario de Elche

Elche, Alicante, Spain

Hospital General Universitario de Elda

Elda, Alicante, Spain

Hospital Municipal de Badalona

Badalona, Barcelona, Spain

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Hospital del Espíritu Santo

Santa Coloma de Gramenet, Barcelona, Spain

Hospital Mutua de Terrassa

Terrassa, Barcelona, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Hospital General Universitario de Vic

Vic, Barcelona, Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital Provincial de Castellón

Castellon, Castellón, Spain

Hospital Universitario Reina Sofía

Córdoba, Cordoba, Spain

Hospital de Jerez de la Frontera

Jerez de la Frontera, Cádiz, Spain

Onkologikoa

Donostia / San Sebastian, Guipúzcoa, Spain

Hosptial Donostia

Donostia / San Sebastian, Guipúzcoa, Spain

Hospital de Barbastro

Barbastro, Huesca, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Hospital Universitario Severo Ochoa

Leganés, Madrid, Spain

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Hospital Universitario San Joan de Reus

Reus, Tarragona, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Centro Oncológico de Galicia

A Coruña, , Spain

Hospital General Universitario de Albacete

Albacete, , Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital Universitario Virgen de los Lirios

Alicante, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Instituto Catalán de Oncología de Girona

Girona, , Spain

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Hospital General Universitario de Guadalajara

Guadalajara, , Spain

Complejo Hospitalario de Jaén

Jaén, , Spain

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital Universitario Lucus Augusti

Lugo, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Clínico Universitario San Carlos

Madrid, , Spain

Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Complejo Hospitalario Unviersitario de Ourense

Ourense, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario de Canarias

Santa Cruz de Tenerife, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario de Valme

Seville, , Spain

Hospital Universitario La Fe

Valencia, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospial General Universitario de Valencia

Valencia, , Spain

Hospital Universitario Arnau de Vilanova de Valencia

Valencia, , Spain

Hospital Provincial Rodríguez Chamorro de Zamora

Zamora, , Spain

Hospital Clínico Universitario de Zaragoza "Lozano Blesa"

Zaragoza, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

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.

Reference Type: RESULT

PMID: 26416999 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35305453 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37338729 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34037241 (View on PubMed)

Related Links

http://www.geicam.org

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

Other Identifiers

GEICAM 2003-10

Identifier Type: -

Identifier Source: org_study_id