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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129935
• Other study ID #: GEICAM 2003-10
• Status: Completed
• Phase: Phase 3
• Start date: February 2004
• Est. completion date: April 4, 2019

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

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1384
• Est. completion date: April 4, 2019
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel

• Capecitabine

• Epirubicin

• Cyclophosphamide

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital General Universitario de Albacete	Albacete
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario Virgen de los Lirios	Alicante
Spain	Hospital Municipal de Badalona	Badalona	Barcelona
Spain	Hospital Universitario Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital de Barbastro	Barbastro	Huesca
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Puerta del Mar	Cádiz
Spain	Hospital Provincial de Castellón	Castellón De La Plana	Castellón
Spain	Hospital Universitario Reina Sofía	Córdoba	Cordoba
Spain	Hosptial Donostia	Donostia-San Sebastián	Guipúzcoa
Spain	Onkologikoa	Donostia-San Sebastián	Guipúzcoa
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital General Universitario de Elda	Elda	Alicante
Spain	Hospital Arquitecto Marcide	Ferrol	A Coruña
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 de Jerez de la Frontera	Jerez De La Frontera	Cádiz
Spain	Hospital Universitario Severo Ochoa	Leganés	Madrid
Spain	Hospital Universitario Arnau de Vilanova de Lleida	Lleida
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro	Majadahonda	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 San Joan de Reus	Reus	Tarragona
Spain	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital del Espíritu Santo	Santa Coloma De Gramenet	Barcelona
Spain	Hospital Universitario de Canarias	Santa Cruz De Tenerife
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospial General Universitario de Valencia	Valencia
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Arnau de Vilanova de Valencia	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Hospital General Universitario de Vic	Vic	Barcelona
Spain	Hospital Provincial Rodríguez Chamorro 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	Hoffmann-La Roche, Pfizer, Sanofi

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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, Andre — View Citation

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 — View Citation

Outcome

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

External Links

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