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

March 3, 2023 updated by: Spanish Breast Cancer Research Group

Phase III Trial to Compare Epirubicin and Cyclophosphamide (EC) Followed by Docetaxel (T) to Epirubicin and Docetaxel (ET) Followed by Capecitabine (X) as Adjuvant Treatment, Node Positive Breast Cancer Patients

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1384

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • A Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruna
      • A Coruña, Spain, 15009
        • Centro Oncológico de Galicia
      • Albacete, Spain, 02066
        • Hospital General Universitario de Albacete
      • Alicante, Spain, 03010
        • Hospital General Universitario de Alicante
      • Alicante, Spain, 03804
        • Hospital Universitario Virgen de los Lirios
      • Barcelona, Spain, 08003
        • Hospital Del Mar
      • Barcelona, Spain, 08036
        • Hospital Clinic I Provincial
      • Barcelona, Spain, 08025
        • Hospital Universitario Santa Creu i Sant Pau
      • Cádiz, Spain, 11009
        • Hospital Universitario Puerta Del Mar
      • Girona, Spain, 17007
        • Instituto Catalán de Oncología de Girona
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves
      • Guadalajara, Spain, 19002
        • Hospital General Universitario de Guadalajara
      • Jaén, Spain, 23007
        • Complejo Hospitalario de Jaen
      • Lleida, Spain, 25198
        • Hospital Universitario Arnau de Vilanova de Lleida
      • Lugo, Spain, 27003
        • Hospital Universitario Lucus Augusti
      • Madrid, Spain, 28040
        • Fundación Jiménez Díaz
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28006
        • Hospital Universitario de La Princesa
      • Madrid, Spain, 28040
        • Hospital Clínico Universitario San Carlos
      • Madrid, Spain, 28021
        • Hospital Universitario 12 de octubre
      • Murcia, Spain, 30120
        • Hospital Universitario Virgen de La Arrixaca
      • Murcia, Spain, 30008
        • Hospital General Universitario Morales Meseguer
      • Málaga, Spain, 29010
        • Hospital Regional Universitario Carlos Haya
      • Málaga, Spain, 29010
        • Hospital Clinico Universitario Virgen de la Victoria
      • Ourense, Spain, 32005
        • Complejo Hospitalario Unviersitario de Ourense
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
      • Santa Cruz De Tenerife, Spain, 38320
        • Hospital Universitario de Canarias
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain, 41014
        • Hospital Universitario de Valme
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncologia
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
      • Valencia, Spain, 46015
        • Hospital Universitario Arnau de Vilanova de Valencia
      • Valencia, Spain, 46014
        • Hospial General Universitario de Valencia
      • Zamora, Spain, 49021
        • Hospital Provincial Rodríguez Chamorro de Zamora
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
      • Zaragoza, Spain, 50009
        • Hospital Clínico Universitario de Zaragoza "Lozano Blesa"
    • A Coruña
      • Ferrol, A Coruña, Spain, 15405
        • Hospital Arquitecto Marcide
    • Alicante
      • Elche, Alicante, Spain, 03203
        • Hospital General Universitario de Elche
      • Elda, Alicante, Spain, 03600
        • Hospital General Universitario de Elda
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitario Germans Trias i Pujol
      • Badalona, Barcelona, Spain, 08911
        • Hospital Municipal de Badalona
      • Sabadell, Barcelona, Spain, 08208
        • Corporacio Sanitaria Parc Tauli
      • Santa Coloma De Gramenet, Barcelona, Spain, 08923
        • Hospital del Espíritu Santo
      • Terrassa, Barcelona, Spain, 08227
        • Consorci Sanitari de Terrassa
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mutua De Terrassa
      • Vic, Barcelona, Spain, 08500
        • Hospital General Universitario de Vic
    • Cantabria
      • Santander, Cantabria, Spain, 39008
        • Hospital Universitario Marques de Valdecilla
    • Castellón
      • Castellón De La Plana, Castellón, Spain, 12002
        • Hospital Provincial de Castellón
    • Cordoba
      • Córdoba, Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia
    • Cádiz
      • Jerez De La Frontera, Cádiz, Spain, 11407
        • Hospital de Jerez de la Frontera
    • Guipúzcoa
      • Donostia-San Sebastián, Guipúzcoa, Spain, 20012
        • Onkologikoa
      • Donostia-San Sebastián, Guipúzcoa, Spain, 20014
        • Hosptial Donostia
    • Huesca
      • Barbastro, Huesca, Spain, 22300
        • Hospital de Barbastro
    • Madrid
      • Alcorcón, Madrid, Spain, 28922
        • Hospital Universitario Fundacion Alcorcon
      • Leganés, Madrid, Spain, 28911
        • Hospital Universitario Severo Ochoa
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro
    • Tarragona
      • Reus, Tarragona, Spain, 43201
        • Hospital Universitario San Joan de Reus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Drug: Docetaxel
Other Names:
  • Taxotere
Drug: Epirubicin
Other Names:
  • Ellence
Drug: Cyclophosphamide
Other Names:
  • cytoxan
Experimental: 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.
Drug: Docetaxel
Other Names:
  • Taxotere
Drug: Epirubicin
Other Names:
  • Ellence
Drug: Capecitabine
Other Names:
  • Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Disease-free Survival (DFS) Event
Time Frame: 5 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Overall Survival (OS) Event
Time Frame: Up to 5 years
A participant was considered to have had a OS event if patient died from any cause.
Up to 5 years
The Number of Participants Who Experienced Adverse Events (AE)
Time Frame: 5 years
Safety was assessed by standard clinical and laboratory tests, and were evaluated using NCI-CTC criteria v2.0
5 years
Quality of Life Questionnaire: Number of Participants With Hair Loss
Time Frame: Up to 24 months

Hair loss was assessed by the quality of life of the patients through the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer 23 (EORTC QLQ-BR23) profile questionnaire, question 4. The quality of life of the patients was evaluated before each cycle and at the end of treatment.

In questionnaire, raw scores range from 0 to 100 and a high score represents a high level of functioning or Health Related Quality of Life, excluding single-item scales in which high scores represent a high level of symptoms. A difference of 10 points on the scale over baseline value was classified as the minimum clinically meaningful change in both questionnaires.
Up to 24 months
Quality of Life Questionnaire: Number of Participants With Hair Loss Recovery
Time Frame: Up to 30 months

Hair Loss Recovery was assessed by a specific Hair Toxicity Questionnaire were patients answered if the hair was less abundant than before, weaker than before or other.

The questionnaire was evaluated up to two years after the end of chemotherapy.
Up to 30 months
Quality of Life Questionnaire: Time to Taking Off the Wig
Time Frame: Up to 30 months

Time to taking off the wig was assessed by a specific Hair Toxicity Questionnaire were patients answered when they stop to use the wig.

The questionnaire was evaluated up to two years after the end of chemotherapy.
Up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spanish Breast Cancer Research Group

Collaborators

Sanofi
Pfizer
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2004

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

April 4, 2019

Study Registration Dates

First Submitted

August 11, 2005

First Submitted That Met QC Criteria

August 11, 2005

First Posted (Estimate)

August 12, 2005

Study Record Updates

Last Update Posted (Actual)

March 31, 2023

Last Update Submitted That Met QC Criteria

March 3, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEICAM 2003-10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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