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
- 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,
- 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
- Age >= 18 and <= 70 years old.
- Performance status (Karnofsky index) >= 80.
- Laboratory results (within 14 days prior to randomization):
- 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.
- 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.
- Prior therapy with anthracyclines or taxanes (paclitaxel or docetaxel) for any
- 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
- Concomitant treatment with other therapy for cancer.