This trial is active, not recruiting.

Condition breast cancer
Treatment capecitabine
Phase phase 3
Sponsor Spanish Breast Cancer Research Group
Collaborator Hoffmann-La Roche
Start date January 2006
End date March 2017
Trial size 876 participants
Trial identifier NCT00130533, CIBOMA 2004-01


This is a prospective, open-label, randomized phase III study. 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
1000 mgrs/m2 twice a day, tablets, 8 cycles
(No Intervention)

Primary Outcomes

Disease free survival
time frame:

Secondary Outcomes

Overall survival
time frame:
Toxicity profile
time frame:
Chemotherapy-related amenorrhea
time frame:
Single nucleotide polymorphisms (SNPs) predicting response to capecitabine
time frame:
5-year disease free survival
time frame:

Eligibility Criteria

Female participants from 18 years up to 70 years old.

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, pN2a, pN3a. - 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 UNL; - SGOT and 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 SNPs 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, pN1c, pN2b, pN3b, pN3c. - Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled HA 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.

Additional Information

Official title Multicenter, Open-label, Randomized Phase III Trial, to Evaluate Efficacy of Maintenance Treatment With Capecitabine (X) Following Standard Adjuvant Chemotherapy, in Operable Breast Cancer Patients With Negative Hormone Receptor, Negative HER2 Tumours
Trial information was received from ClinicalTrials.gov and was last updated in July 2015.
Information provided to ClinicalTrials.gov by Spanish Breast Cancer Research Group.