Maintenance Treatment With Capecitabine Versus Observation in Breast Cancer Patients

NCT ID: NCT00130533

Last Updated: 2023-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 876 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2017-02-17

Brief Summary

This is a prospective, open-label, randomized phase III study assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer.

Detailed Description

Patients will be stratified as per investigational site, previous adjuvant chemotherapy (anthracyclines versus anthracyclines plus taxanes), and number of affected axillary lymph nodes (0, 1-3, >= 4). Node negative patients must present a tumour size > 2 cm to be eligible. At least 6 lymph nodes must be analysed to confirm the number of affected nodes. Patients will be randomised to receive: 8 courses of capecitabine 1000 mg/m2 by mouth, twice a day (p.o. bid) for 14 days, followed by a 7 day rest versus observation.

Tissue samples must be analysed by a central laboratory, to confirm estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2), cytokeratins (CK) 5/6 and epidermal growth factor receptor (EGFR) status.

The following data were obtained from the database of the "El Alamo" project. One thousand six hundred and twenty-seven (1,627) in total were considered during the years 1990 to 1997. The population is formed of patients with operable breast cancer, with surgery, positive nodes, and negative hormone receptors, or negative nodes, negative hormone receptors and T2-3 tumors.

For these patient groups, estimated 5-year disease-free survival is 64.72%. Assuming an exponential distribution, the aim is to detect an increase of 64.72% to 73.7% in 5 years Disease Free survival rate corresponds to a Hazard Ratio of 0.701 and a risk reduction of about 30%, with a power of 80% using a two-tailed log-rank test at 0.05 and whereas 4 years of recruitment period and 3 years of follow-up period. We would need 255 events, 834 patients without considering any dropouts.

Considering a drop-out rate of 5% post-randomization, the final sample size will be 876 patients, 438 per treatment arm.

The sample size calculation was performed by the program package "EAST" version 5.2.

Conditions

Breast Cancer

Study Design

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

Study Groups

Xeloda (capecitabine)

1000 mgrs/m2 twice a day, tablets, 8 cycles

Group Type: EXPERIMENTAL

Capecitabine

Intervention Type: DRUG

Observation

Observation. No intervention.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Capecitabine

Intervention Type: DRUG

Other Intervention Names

Xeloda

Eligibility Criteria

Inclusion Criteria

• Written informed consent.
• Histological diagnoses of operable invasive adenocarcinoma of the breast (T1-T3). Tumours must be HER2 negative. Time window between end of adjuvant chemotherapy and study randomization must be less than 8 weeks. In patients receiving adjuvant radiotherapy, time window allowed between last session and randomisation is 4 weeks.
• Surgery must consist of mastectomy or conservative surgery with axillary lymph node dissection. Margins free of disease and ductal carcinoma in-situ (DCIS) are required. Lobular carcinoma is not considered a positive margin.
• Node negative patients with tumour size > 2 cm.
• Positive axillary lymph nodes defined as at least 1 out of 6 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: pN1a (Metastases in 1-3 axillary lymph nodes, at least one metastasis greater than 2.0 mm), pN2a (Metastases in 4-9 axillary lymph nodes (at least one tumor deposit greater than 2 mm)), pN3a (Metastases in 10 or more axillary lymph nodes [at least one tumor deposit greater than 2 mm]; or metastases to the infraclavicular [level III axillary lymph] nodes).
• Status of hormone receptors in primary tumour. Negative results must be available before the end of adjuvant chemotherapy.
• Patients must not present evidence of metastatic disease.
• Negative status of HER2 in primary tumour, known before randomization.
• Adjuvant chemotherapy consisting of a minimum of 6 courses with anthracyclines and/or taxanes.
• Age >= 18 and <= 70 years old.
• Performance status (Karnofsky index) >= 80.
• Laboratory results (within 14 days prior to randomization):
• Hematology:

• neutrophils >= 1.5 x 10e9/l;
• platelets >= 100x 10e9/l;
• hemoglobin >= 10 mg/dl
• Hepatic function:

• total bilirubin <= 1 upper normal limit (UNL);
• Aspartate aminotransferase (AST or SGOT) and Alanine aminotransferase (ALT or 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 µmol/l (2 mg/dl).
• creatinine clearance >= 60 ml/min.
• Pharmacogenetics:

• one blood sample is needed for single nucleotide polymorphism (SNP) assessment.
• Patients able to comply with treatment and study follow-up.
• Negative pregnancy test done in the 14 previous days to randomization.

Exclusion Criteria

• Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any malignancy.
• Pregnant or lactating women. Adequate contraceptive methods must be used during chemotherapy and hormone therapy treatments. Negative pregnancy test in the 14 previous days to randomization.
• Bilateral invasive breast cancer.
• Any T4 or M1 tumour.
• Axillary lymph nodes: patients belonging to the following classifications are excluded: pN1b (Metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN1c (Metastases in 1-3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN2b (Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases), pN3b (Metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes; or in more than three axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected), pN3c (Metastases in ipsilateral supraclavicular lymph nodes).
• 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 to free informed consent.
• Active uncontrolled infection.
• Active peptic ulcer, unstable diabetes mellitus.
• Previous or current history of neoplasms different to 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.
• History of hypersensitivity to capecitabine, fluorouracil.
• Patients lacking physical integrity of upper gastrointestinal tract or with history of bad absorption syndrome.
• History of dihydropyrimidine dehydrogenase (DPD) deficiency.
• Anticoagulant treatment with coumadin anticoagulants.
• Current treatment with sorivudine or its chemical family.
• Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 30 previous days before randomization.
• Concomitant treatment with other therapy for cancer.
• Males.

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

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

IBEROAMERICAN COALITION FOR BREAST ONCOLOGY RESEARCH (CIBOMA)

UNKNOWN

Sponsor Role: collaborator

Spanish Breast Cancer Research Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Principal Investigator

Role: PRINCIPAL_INVESTIGATOR

Hospital Clínico Universitario de Valencia

Locations

Hospital General Universitario de Elche

Elche, Alicante, Spain

Instituto Catalán de Oncología de L'Hospitalet

L'Hospitalet de Llobregat, Barcelona, Spain

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, Spain

Hospital del Espíritu Santo

Santa Coloma de Gramenet, Barcelona, Spain

Consorci Sanitari de Terrassa

Terrassa, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital Provincial de Castellón

Castellon, Castellón, Spain

Hospital General de Jerez

Jerez de la Frontera, Cádiz, Spain

Onkologikoa

Donostia / San Sebastian, Guipúzcoa, Spain

Hospital de Donostia

Donostia / San Sebastian, Guipúzcoa, Spain

Hospital de Barbastro

Barbastro, Huesca, Spain

Hospital Insular de Las Palmas de Gran Canaria

Las Palmas de Gran Canaria, Las Palmas, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Coalición Iberoamericana de Investigación en Oncología Mamaria (CIBOMA)

San Sebastián de los Reyes, Madrid, Spain

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Centro Oncológico de Galicia

A Coruña, , Spain

Hospital Universitario General de Alicante

Alicante, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Hospital Universitario Germans Trias i Pujol

Barcelona, , Spain

Hospital Universitario General Yagüe

Burgos, , Spain

Hospital Universitario Puerta del Mar

Cadiz, , Spain

Hospital Universitario Reina Sofía

Córdoba, , 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 La Princesa

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Ruber Internacional

Madrid, , Spain

Hospital Clínico Universitario San Carlos

Madrid, , Spain

Hospital de Madrid Norte Sanchinarro (CIOCC)

Madrid, , Spain

Hospital Universitario Virgen de la Arrixaca

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital General Universitario Morales Meseguer

Murcia, , Spain

Complejo Hospitalario de Ourense

Ourense, , Spain

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Nuestra Señora de Candelaria

Santa Cruz de Tenerife, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario de Valme

Seville, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital General Universitario de Valencia

Valencia, , Spain

Hospital Provincial de Zamora "Rodríguez Chamorro"

Zamora, , Spain

Hospital Clínico Universitario de Zaragoza "Lozano Blesa"

Zaragoza, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Countries

Spain

References

Lluch A, Barrios CH, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Guerrero-Zotano A, Garcia-Saenz JA, Torres R, de la Haba J, Garcia-Martinez E, Gomez HL, Llombart A, Bofill JS, Baena-Canada JM, Barnadas A, Calvo L, Perez-Michel L, Ramos M, Fernandez I, Rodriguez-Lescure A, Cardenas J, Vinholes J, Martinez de Duenas E, Godes MJ, Segui MA, Anton A, Lopez-Alvarez P, Moncayo J, Amorim G, Villar E, Reyes S, Sampaio C, Cardemil B, Escudero MJ, Bezares S, Carrasco E, Martin M; GEICAM Spanish Breast Cancer Group; CIBOMA (Iberoamerican Coalition for Research in Breast Oncology); LACOG (Latin American Cooperative Oncology Group). Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01). J Clin Oncol. 2020 Jan 20;38(3):203-213. doi: 10.1200/JCO.19.00904. Epub 2019 Dec 5.

Reference Type: RESULT

PMID: 31804894 (View on PubMed)

Schettini F, Chic N, Braso-Maristany F, Pare L, Pascual T, Conte B, Martinez-Saez O, Adamo B, Vidal M, Barnadas E, Fernandez-Martinez A, Gonzalez-Farre B, Sanfeliu E, Cejalvo JM, Perrone G, Sabarese G, Zalfa F, Peg V, Fasani R, Villagrasa P, Gavila J, Barrios CH, Lluch A, Martin M, Locci M, De Placido S, Prat A. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021 Jan 4;7(1):1. doi: 10.1038/s41523-020-00208-2.

Reference Type: RESULT

PMID: 33397968 (View on PubMed)

Asleh K, Lluch A, Goytain A, Barrios C, Wang XQ, Torrecillas L, Gao D, Ruiz-Borrego M, Leung S, Bines J, Guerrero-Zotano A, Garcia-Saenz JA, Cejalvo JM, Herranz J, Torres R, Haba-Rodriguez J, Ayala F, Gomez H, Rojo F, Nielsen TO, Martin M. Triple-Negative PAM50 Non-Basal Breast Cancer Subtype Predicts Benefit from Extended Adjuvant Capecitabine. Clin Cancer Res. 2023 Jan 17;29(2):389-400. doi: 10.1158/1078-0432.CCR-22-2191.

Reference Type: RESULT

PMID: 36346687 (View on PubMed)

Ye F, Bian L, Wen J, Yu P, Li N, Xie X, Wang X. Additional capecitabine use in early-stage triple negative breast cancer patients receiving standard chemotherapy: a new era? A meta-analysis of randomized controlled trials. BMC Cancer. 2022 Mar 12;22(1):261. doi: 10.1186/s12885-022-09326-5.

Reference Type: RESULT

PMID: 35279130 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.ciboma.org/

Sponsor's web

http://www.geicam.org/

Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

Other Identifiers

2005-002838-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CIBOMA 2004-01

Identifier Type: -

Identifier Source: org_study_id