Female breast cancer patients with progression of brain metastasis following WBRT and at least one measurable lesion in the brain (defined as any lesion >1 cm in longest dimension at MRI). MedDRA version: 9.1 Level: LLT Classification code 10006128 Term: Brain metastases
Conditions
Interventions
Trade Name: Xeloda
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
Current Sponsor code: RO 09-1978
Other descriptive name: 5'-desoxy-5fluoro-N4-(pentyloxy carbonyl cytidine)
Sponsors
ROCHE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must have signed a written informed consent form prior to any study specific screening procedures • Women • 18 years or older • ECOG Performance Status 0-2 • Life expectancy = 3 months • Able to comply with the protocol • Patient affiliated to the national “Social Security” regimen or beneficiary of this regimen • Able to swallow oral medications • Histologically confirmed breast cancer • HER2 and hormone receptors status known • Brain metastasis progression after whole brain radiotherapy alone or radio-surgery + whole brain radiotherapy with at least one measurable lesion in the brain (defined as any lesion =1 cm on T1-weighted contrast enhanced MRI) • Stable extra-cranial disease • Patients could entered in the study regardless of previous treatment (included chemotherapy except capecitabine) for metastatic extracranial disease • No steroids or stable dose of steroids for at least 5 days before the MRI evaluation • Adequate hematologic function: Absolute neutrophil count =1.5 x 109/L and platelets = 100 x 109/L and Hb = 9 g/Dl • Adequate liver function: Total bilirubin = 1.5 x ULN and AST or ALT = 2.5 x ULN (= 5 x ULN in patients with liver metastases) • Adequate renal function: Serum creatinine = 1.5 x ULN or Creatinine clearance = 50 mL/min (Cockroft Gault formula) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Prior treatment with capecitabine • Leptomeningeal disease • Previous history of cancer (other than curatively treated basal and squamous cell carcinoma of the skin and/or in-situ carcinoma of the cervix) within the 5 years before study entry • Pregnant or breast feeding women • Women with an intact uterus (unless amenorrhoeic for the last 24 months) not using effective means of contraception • Patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up • Clinically significant malabsorption syndrome or inability to take oral medication • Clinically significant (i.e. active) cardiovascular disease, i.e. myocardial infarction within the last 6 months before inclusion, unstable angina, congestive heart failure NYHA Class = II, serious cardiac arrhythmia requiring medication during the study which might interfere with regularity of the study treatment or not controlled by medication • Evidence of ongoing or active infection (requiring IV antibiotics), any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or increases the patient’s risk of treatment-related complications • Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogue such as brivudine • Treatment with any other investigational agent within 30 days prior to enrolment • Prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency) or known allergy to capecitabine, to 5-fluorouracil, to other study therapies or any of their excipients • Known DPD deficiency • History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents or other contraindication to MRI (cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of capecitabine in terms of Progression Free Survival (PFS) rate at 4 months, reviewed by centralized independent expert, in treatment of brain metastases secondary to breast cancer in patients with CNS progression after whole brain radiotherapy (WBRT) ;Secondary Objective: To evaluate the following parameters: - Objective CNS response (CR+PR) - Duration of CNS response - CNS progression-free survival - Progression-free survival assessed by investigator - Disease control rate defined as Overall Response (CR+PR) + Stable Disease (SD) for overall disease - Overall survival - Safety according to CTC-AE v3.0 and with the Mini Mental Score (MMS) examination to evaluate the neurotoxicity ;Primary end point(s): The primary criterion is Progression Free Survival Rate at 4 months (16 weeks). Progression Free Survival is defined as the time from the first administration of study treatment to CNS or extra-cranial disease progression according to RECIST criteria reviewed by centralized independent expert or death from any cause. The CNS assessments will be realized by contrast-enhanced MRI and the extra-cranial disease assessments will be realized by CT Chest/Abdomen/Pelvis. | — |
Countries
France
Outcome results
None listed