Maintenance Treatment With Capecitabine Versus Observation in Breast Cancer Patients

Breast Cancer Clinical Trial

Official title:

Multicenter, Open-label, Randomized Phase III to Evaluate Efficacy of Maintenance Treatment With Capecitabine Following Standard Adjuvant Chemotherapy in Operable Triple Negative Breast Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130533
• Other study ID #: CIBOMA 2004-01
• Secondary ID: 2005-002838-36
• Status: Completed
• Phase: Phase 3
• Start date: January 2006
• Est. completion date: February 17, 2017

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 876
• Est. completion date: February 17, 2017
• Est. primary completion date: February 17, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Capecitabine

Locations

Country	Name	City	State
Spain	Centro Oncológico de Galicia	A Coruña
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Universitario General de Alicante	Alicante
Spain	Hospital de Barbastro	Barbastro	Huesca
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitario Germans Trias i Pujol	Barcelona
Spain	Hospital Universitario General Yagüe	Burgos
Spain	Hospital Universitario Puerta del Mar	Cádiz
Spain	Hospital Provincial de Castellón	Castellón De La Plana	Castellón
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital de Donostia	Donostia-San Sebastián	Guipúzcoa
Spain	Onkologikoa	Donostia-San Sebastián	Guipúzcoa
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital General Universitario de Guadalajara	Guadalajara
Spain	Complejo Hospitalario de Jaén	Jaén
Spain	Hospital General de Jerez	Jerez De La Frontera	Cádiz
Spain	Instituto Catalán de Oncología de L'Hospitalet	L'Hospitalet De Llobregat	Barcelona
Spain	Hospital Insular de Las Palmas de Gran Canaria	Las Palmas De Gran Canaria	Las Palmas
Spain	Hospital Universitario Arnau de Vilanova de Lleida	Lleida
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital de Madrid Norte Sanchinarro (CIOCC)	Madrid
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Princesa	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	Corporació Sanitaria Parc Taulí	Sabadell	Barcelona
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
Spain	Coalición Iberoamericana de Investigación en Oncología Mamaria (CIBOMA)	San Sebastián de los Reyes	Madrid
Spain	Hospital del Espíritu Santo	Santa Coloma De Gramenet	Barcelona
Spain	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz De Tenerife
Spain	Hospital Universitario Marqués 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 Virgen de la Salud	Toledo
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital General Universitario de Valencia	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
Spain	Complejo Hospitalario Universitario de Vigo	Vigo	Pontevedra
Spain	Hospital Provincial de Zamora "Rodríguez Chamorro"	Zamora
Spain	Hospital Clínico Universitario de Zaragoza "Lozano Blesa"	Zaragoza
Spain	Hospital Universitario Miguel Servet	Zaragoza

Sponsors (3)

Lead Sponsor	Collaborator
Spanish Breast Cancer Research Group	Hoffmann-La Roche, IBEROAMERICAN COALITION FOR BREAST ONCOLOGY RESEARCH (CIBOMA)

Country where clinical trial is conducted

Spain, 

References & Publications (4)

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 — View Citation

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, Fernande — View Citation

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, Bar — View Citation

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):26 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Free Survival (DFS) Events	DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.	5 years
Secondary	Disease Free Survival (DFS) Events by Phenotype	DFS was measured from the date of randomization assignment in the intent to treat (ITT) population to loco-regional or distant recurrence, second primary malignancy or death date, whichever occurred first.	5 years
Secondary	Overall Survival (OS) Event	OS event is defined as the death from any cause.	5 years
Secondary	The Number of Participants Who Experienced Adverse Events (AE)	Safety will be assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events).	5 years

External Links

•   Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group
•   Sponsor's web