Female breast cancer patients with newly diagnosed CNS metastases with at least one brain lesion measuring =0.5 cm in longest dimension, who are not considered candidates for surgery or stereotactic radio-surgery or who refuse surgery or stereotactic radio-surgery MedDRA version: 9.1 Level: LLT Classification code 10006128 Term: Brain metastases
Conditions
Interventions
Trade Name: Xeloda®
Product Code: RO 09-1978
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Current Sponsor code: RO 09-1978
Other descriptive name:
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 • Newly diagnosed CNS metastasis with at least one measurable lesion in the brain (defined as any lesion > 0.5 cm on T1-weighted contrast enhanced MRI) • Patients could entered in the study regardless of previous treatment (included chemotherapy) for metastatic extracranial disease • A previous exposure to capecitabine is allowed unless appearance of brain metastases during the capecitabine or if capecitabine considered inappropriate by investigator • Patient not eligible for or refusing surgery or stereotactic radiosurgery • No steroids or stable or decreasing dose of steroids for a 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 =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Prior treatment of brain metastases • 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 • Severe resting dyspnea • 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 • Patient with known contra-indication to radiotherapy. • Treatment with any other investigational agent within 30 days prior to enrolment. • Concurrent use of Lapatinib during the treatment period (induction treatment with WBRT +/- capecitabine and maintenance treatment with capecitabine or standard of care) • 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 demonstrate the superiority of WBRT with concurrent capecitabine followed by maintenance capecitabine versus WBRT in best objective CNS response (CR + PR) in breast cancer patients with newly diagnoses CNS metastasis;Secondary Objective: To compare the following parameters between the 2 study Arms: - Objective CNS response (CR+PR) at 4 weeks post-WBRT - Clinical Benefit defined as CNS response (CR+PR) + Stable Disease (SD) - Duration of CNS response - Brain progression-free survival - Extra-cranial disease response rate - Progression-free survival - 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): Best Objective CNS response rate (CR+PR) measured from the start of study treatment administration until documented CNS recurrence or progression assessed by contrast-enhanced MRI reviewed by centralized independent expert and defined as already describe | — |
Countries
France
Outcome results
None listed