Health Condition 1: null- Metastatic Breast Cancer
Conditions
Interventions
Intervention1: Trastuzumab-MCC-DM1: T-DM1 3.6 mg/kg intravenously (IV) over 30−
90 minutes on Day 1 of a 21-day cycle
Duration : Progressive Disease or until death, whichever occurs first.
Control Intervention1: Capecitabine + Lapatinib: Lapatinib 1250 mg/day orally once per day
14 of a 21-day cycle
Duration : Progressive Disease or until death, whichever occurs first.
Sponsors
Genentech Inc
F Hoffmann La Roche Ltd
Eligibility
Inclusion criteria
Inclusion criteria: There is no upper age limit in the trial 1. HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results 2. Histologically or cytologically confirmed invasive breast cancer 3. Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include both: a taxane, alone or in combination with another agent, and trastuzumab alone or in combination with another agent 4. Documented progression of incurable, unresectable, locally advanced or metastatic breast cancer, defined by the investigator 5. Measurable and/or nonmeasurable disease; patients with central nervous system (CNS)-only disease are excluded 6. Cardiac ejection fraction ¡Ý50% by either ECHO or MUGA 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 8. For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception; contraception use should continue for the duration of the study treatment and for at least 6 months after the last dose of study treatment
Exclusion criteria
Exclusion criteria: 1. History of treatment with T-DM1 2. Prior treatment with lapatinib or capecitabine 3. Peripheral neuropathy of Grade ¡Ý3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 4. History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer, or cancers with a similar curative outcome as those mentioned above 5. History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to randomization except hormone therapy, which can be given up to 7 days prior to randomization; recovery of treatment-related toxicity consistent with other eligibility criteria 6. History of radiation therapy within 14 days of randomization 7. Brain metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 2 months (60 days) of randomization 8. History of symptomatic congestive heart failure (CHF) or serious cardiac arrhythmia requiring treatment 9. History of myocardial infarction or unstable angina within 6 months of randomization 10. Current dyspnea at rest due to complications of advanced malignancy or current requirement for continuous oxygen therapy 11. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) 12. Pregnancy or lactation 13. Current known active infection with HIV, hepatitis B virus, or hepatitis C virus 14. Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis 15. History of intolerance (such as Grade 3-4 infusion reaction) to trastuzumab 16. Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency 17. Current treatment with sorivudine or its chemically related analogs, such as brivudine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Incidence, nature, and severity of adverse events 2. Overall survival and landmark survival rate 3. Progression-free survival (PFS) by Independent Review Committee assessmentTimepoint: 1. Through study completion or early study discontinuation 2. Time from randomization to death 3. Time from randomization to the first occurrence of progression or death The expected end of the study is Nov-2013. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To compare the overall ORR between the two treatment arms on the basis of both investigator and independent review of tumor assessments 2. To estimate the duration of objective response within each treatment arm on the basis of both investigator and independent review of tumor assessments 3. To compare PFS between the two treatment arms on the basis of investigator review of tumor assessmentsTimepoint: 1. Confirmed response at least 28 days after initial documentation of response 2. First occurrence of a documented objective response until the time of disease progression 3. Time from randomization to the first occurrence of progression or death | — |
Countries
Brazil, Bulgaria, Canada, Colombia, Denmark, Finland, France, Germany, India, Italy, Mexico, Poland, Portugal, Republic of Korea, Russian Federation, Singapore, Slovenia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States of America
Contacts
Public ContactAnil Kukreja
Outcome results
None listed