Patient with non penetrated brain metastasis from HER2 positive breast cancer. MedDRA version: 9.1 Level: LLT Classification code 10006128 Term: Brain metastases
Conditions
Interventions
Trade Name: Tyverb® 250mg
Product Name: Lapatinib
Pharmaceutical Form: Coated tablet
Trade Name: Xeloda® 150mg
Product Name: Capécitabine
Pharmaceutical Form: Coated tablet
Trade Name: Xeloda® 500mg
Sponsors
FNCLCC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed invasive breast cancer with stage IV disease. 2. HER-2 positive primary tumor, defined as : IHC3+, or IHC2+ and FISH positive. 3. At least one measurable CNS lesion = 10 mm on T1-weighted gadolinium-enhanced MRI. 4. At least two weeks from any specific breast cancer treatment (such as Trastuzumab, chemotherapy, immunotherapy/biological response modifiers, endocrine therapy and radiotherapy). 5. Adequate hematologic function (ANC = 1.0x109/L, platelets = 100 000 ; Hb = 10g/l), renal function (creatinine = 1.5 UNL) and hepatic function (albumin = 2.5 g/dL ; serum bilirubin = 1.5x ULN unless due to Gilbert’s syndrome ; ASAT and ALAT = 5x ULN if documented liver metastases or = 3x ULN without liver metastases) 6. Patients able to swallow and retain oral medication. 7. At least 18 years old. 8. ECOG Performance Status of 0 to 2. 9. Life expectancy = 3 months. 10. Potentially reproductive patients must agree to use an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product for women. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment. 11. Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or urine pregnancy test 48 hours prior to the administration of the first study treatment. 12. Patients must be affiliated to a Social Security System. 13. Patient information and written informed consent form signed. 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: 1) Previous whole brain radiotherapy (WBRT) or brain stereotactic radiotherapy. 2) Planned or concurrent systemic treatment or radiation therapy for breast cancer (other that corticosteroid, biphosphonates or mannitol). 3) Single brain metastasis which could be treated by surgery. 4) Known contra-indication to MRI. 5) Active concurrent malignancy. If there is a history of prior malignancy, the patient must be disease free for at least 10 years. 6) Previous treatment with capecitabine, and/or lapatinib. 7) Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as : a) infection, b) cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF > grade 2, c) current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment), d) renal disease, e) active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded, f) severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation of 88% or less at rest on room air). 8) Known dihydropyrimidine dehydrogenase (DPD) deficiency. 9) Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Clarithromycin, Ketoconazole, Itroconazole, Voriconazole, Ritonavir, etc.)within the last 7 to 14 days prior to inclusion and/or during the study. 10) Pregnant women, women who are likely to become pregnant or are breast-feeding. 11) Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. 12) Patients who received any other investigational drugs within the 30 days prior to the screening visit. 13) Individual deprived of liberty or placed under the authority of a tutor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the objective response rate by volumetric analysis of the combination lapatinib and capecitabine on brain metastasis as assessed by MRI, in metastatic HER2 positive breast cancer patients, prior to any brain radiotherapy.;Secondary Objective: - To document any toxicity evaluated by NCI-CTC-V3.0. - To assess the time to radiotherapy - To document the time to disease progression in the central nervous system (CNS). - To evaluate the overall response rate for extra-CNS disease. - To assess the clinical benefit (complete response [CR], partial response [PR], and stable disease [SD] for at least 6 months) for both CNS and extra-CNS disease.;Primary end point(s): CNS objective response rate is the primary study endpoint, where CNS objective response is defined as either a CR or PR, assessed by centralized volumetric analyses of magnetic resonance imaging (MRI), provided there is no progression of systemic disease outside of the CNS, increasing steroid requirements, or worsening of neurological signs and symptoms (NSS). MRI for volumetric assessments will be performed every 6 weeks according to protocol specific acquisition guidelines (appendix 12). If a CNS PR or CR is assigned following an MRI scan of the brain, a follow-on disease assessment by MRI should be performed approximately 4 weeks after the criteria for response are first met, and then repeated once more, 4 weeks later. | — |
Countries
France
Outcome results
None listed