Metastatic breast cancer overexpressing ErbB2 MedDRA version: 19.0 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: As the study was stopped on 11th June 2012, No further subjects will be enrolled.: 1. Able to give signed written informed consent 2. Females age = 18 years old 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; 4. Life expectancy of at least 12 weeks 5. Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease. 6. ErbB2 overexpression in the invasive component of the primary or metastatic lesion as locally defined by: • 3+ staining by immunohistochemistry (IHC); • or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH,CISH or SISH; • ErbB2 gene amplification by FISH, CISH or SISH HER2/neu gene amplification by fluorescence, chromogenic or silver in situ hybridization [FISH, CISH or SISH; >6 HER2/neu gene copies per nucleus or a FISH, CISH or SISH test ratio (HER2 gene copies to chromosome 17 signals) of =2.0] • subjects with a negative or equivocal overall result are not eligible for participation in the trial. 7. Subjects must have evidence of metastatic disease, but measurable disease is not mandatory. NOTE: Pleural effusion or ascites (without cytologic verification) as the only evidence of metastatic disease do not meet the eligibility criteria. 8. Prior treatment with taxanes or anthracyclines is required. All treatment related adverse events must be = Grade 1 at the time of randomization 9. Prior treatment with other chemotherapeutic agents is permitted provided that all treatment related adverse events are = Grade 1 at the time of randomization 10. Prior treatment with trastuzumab is permitted provided that at least 6 weeks has elapsed since the last dose of therapy and all treatment related adverse events are = Grade 1 at the time of randomization 11. Prior treatment with endocrine therapy is permitted provided that therapy has been discontinued and all treatment related adverse events are = Grade 1 at the time of randomization 12. Prior treatment with radiation therapy is permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are = Grade 1 at the time of randomization 13. Baseline LVEF = 50% and not lower than the institutional lower limit of normal measured by echocardiography or MUGA scan; NOTE: The same modality used at baseline must be used for repeat assessment throughout study 14. Concurrent treatment with bisphosphonates is permitted; however treatment must be initiated prior to the first dose of study therapy 15. Able to swallow and retain oral medications; 16. A female who is of: • non-childbearing potential, including any female who has had hysterectomy, a bilateral oopheroctemy, bilateral tubular ligation or is post-menopausal (total cessation of menses for = 1 year • childbearing potential who must have a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception (for example, intrauterine device [IUD], birth control pills unless clinically contraindicated, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product. 17. Subjects must complete all screening assessments as outlined in the protocol 18. Subjects must have normal organ and marrow function. Are the trial subjects under 18? no Nu
Exclusion criteria
Exclusion criteria: As the study was stopped on 11th June 2012, No further subjects will be enrolled.: 1. History and/or current evidence of CNS metastases (including leptomeningeal involvement). or evidence of benign or malignant brain tumors and/or evidence of spinal cord metastases at Baseline. Any evidence of brain metastases on Baseline MRI scan (performed within 4 weeks prior to randomization) as determined by Independent Reviewer; 2. Concurrent treatment with an investigational agent or participation in another treatment clinical trial 3. Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab(including but not limited to trastuzumab-DM1 and neratinib); 4. Prior treatment with capecitabine 5. Known dihydropyrimidine dehydrogenase (DPD) deficiency 6. ECOG Performance Status >2 7. Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy (including an ErbB1 and/or ErbB2 inhibitor), or hormonal therapy for treatment of cancer 8. History of allergic reactions attributed to compounds of similar chemical composition to lapatinib (quinazolines) 9. History of allergic reactions attributed to compounds chemically related to capecitabine, fluorouracil or any excipients 10. Concurrent treatment with medications listed in Section 4.11.2, Prohibited Medications and Non-Drug Therapies; 11. Concomitant use of CYP3A4 inhibitors or inducers 12. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel 13. History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast 14. Compromised renal function that would exclude subjects from receiving gadolinium based contrast agents as guided by local institutional policy 15. Other known contraindication to MRI, such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel 16. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the subject's safety or compliance to study procedures 17. Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment); 18. Any on-going toxicity from prior anti cancer therapy that is > Grade 1 and/or is progressing in severity except alopecia; 19. Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent, unless a legally acceptable representative could provide informed consent 20. Active cardiac disease, defined as one or more of the following: • History of uncontrolled or symptomatic angina • History of arrhythmias requiring medications, or clinically significant • Myocardial infarction < 6 months from study entry • Uncontrolled or symptomatic congestive heart failure • Cardiac angioplasty or stenting • Ejection fraction below the institutional normal limit • History of documented congestive heart failure (CHF) or systolic dysfunction; • Clinically significant valvular heart disease • Any other cardiac condition, which in the opinion of the treating physician would make this protocol unreasonably hazardous for the patient. 21. Unc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of lapatinib plus capecitabine on incidence of CNS as site of first relapse as compared with trastuzumab plus capecitabine;Secondary Objective: To evaluate and compare the two treatment arms for the following: • Progression free survival • Time to first CNS progression • Overall survival • Overall response rate (CR or PR) • Clinical benefit response rate (confirmed CR or PR at any time or SD for = 24 weeks ) • Duration of response • Incidence of CNS progression at any time (brain scans will not be required following non-CNS progression; therefore incidence of CNS progression at any time will include progression documented by brain scan on study as well as CNS progression as indicated by the investigator on follow-up eCRF page). • The qualitative and quantitative toxicities.;Primary end point(s): As the study was stopped on 11th June 2012, No further subjects will be enrolled 2012 after IDMC review of the IA. Incidence of CNS as site of first relapse will be the primary endpoint of this study. CNS disease progression will be assigned using protocoldefined criteria as specified in Section 5.2.3.2 and analysis will be done on M-ITT (modified intent-to- treat) population as defined in Section 7.3.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression Free Survival (PFS) which is defined as time from randomization to the time of first documented disease progression at any site or death due to any cause. • Overall Survival (OS), which is defined as the time from randomization until death due to any cause. • Time to first CNS progression, which is defined as the time from randomization until documented CNS progression. • Overall Response Rate, which is defined as percent of subjects experiencing confirmed Complete Response (CR) and Partial Response (PR) • Clinical Benefit Response Rate, which is defined as percentage of subjects experiencing confirmed CR or PR at any time or Stable Disease (SD) for =24 weeks. • Duration of Response, which is defined as the time from first objective response (CR or PR) until tumor progression at any site or death due to breast cancer. • Incidence of CNS progression at any time, defined as the proportion of subjects who have relapsed with brain metastases at any time regardless of whether or not progression has been documented via radiological scan. Subjects who have not relapsed at the time of analysis will be included in the denominator. | — |
Countries
Belgium, Denmark, France, Germany, Greece, Hungary, Italy, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma Services AG
Outcome results
None listed