HER2-positive metastatic breast cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Interventions
Product Name: Trastuzumab-MCC-DM1
Product Code: T-DM1, RO05304020
Pharmaceutical Form: Powder for concentrate for solution for infusion
CAS Number: 1018448-65-1
Current Sponsor code: RO05304020
Other
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. Disease-Specific Criteria 1. Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy. Patients with locally advanced disease must have recurrent or progressive disease after failing initial attempts at local control. The disease must be considered to be unresectable. 2. HER2-positive (IHC 3+ or FISH-positive) based on local laboratory assay results 3. No prior chemotherapy for their MBC (hormonal therapy is allowed) 4. Measurable disease per modified RECIST Patients should have at least one target lesion =2 cm on conventional CT scan or = 1 cm on a spiral CT scan. 5. Tumor blocks or 11 unstained slides available for confirmatory central laboratory HER2 testing b. General Criteria 6. Age =18 years 7. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 8. Adequate organ function, evidenced by the following laboratory results within approximately 21 days prior to randomization: Absolute neutrophil count >1500 cells/mm[3] Platelet count > 100,000 cells/mm[3] Hemoglobin > 9.0 g/dL Patients are allowed to be transfused with red blood cells to obtain this level Total bilirubin = 1.5 x the upper limit of normal (ULN) SGOT (AST) and/or SGPT (ALT) and alkaline phosphatase = 2.5 ×ULN, with the following exception: Patients with bone metastases: alkaline phosphatase =5 ×ULN Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: a. Cancer-Related Criteria 1. History of any chemotherapy for MBC Prior hormonal therapy is allowed 2. An interval of 500 mg/m[2] Epirubicin > 900 mg/m[2] Mitoxantrone > 120mg/m[2] and idarubicin > 90 mg/m[2] If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m[2] of doxorubicin. b. Cardiopulmonary Function 10. Current unstable angina 11. History of symptomatic congestive heart failure (CHF; New York Heart Association [NYHA] classes II-IV), or ventricular arrhythmia requiring treatment 12. History of myocardial infarction within 6 months prior to randomization 13. LVEF below 50% within approximately 28 days prior to randomization 14. History of a decrease in LVEF to < 40% or symptomatic CHF with previous adjuvant trastuzumab treatment 15. Cardiac troponin I = 0.2 ng/mL within approximately 28 days prior to randomization 16. Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy General Criteria 17. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures) 18. Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment 19. Current pregnancy or lactation 20. History of receiving any investigational treatment within approximately 28 days prior to randomization 21. Current known infection with HIV, active hepatitis B and/or hepatitis C virus 22. History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel 23. Known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate 80 24. Assessed by the investigator to be unable or un
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives for this study are as follows: • To explore the efficacy of T-DM1 compared with the combination of trastuzumab and docetaxel in patients with HER2-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease, as measured by PFS based on investigator assessments • To evaluate the safety of T-DM1 compared with the combination of trastuzumab and docetaxel in this population;Secondary Objective: The secondary objectives of this study are as follows: • To explore the efficacy of T-DM1 compared with the combination of trastuzumab and docetaxel in patients with HER2-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease, as measured by the 12-month PFS rate, median PFS, duration of overall survival, survival rate at 12 months, objective response rate, duration of objective response, and clinical benefit rate (the proportion of patients with CR or PR or stable disease for =6 months since randomization). • To characterize the PK properties of T-DM1 in this patient population • To compare the time to symptom progression, as measured by the Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) and the Patient's Assessment of Pain, in the two treatment arms;Primary end point(s): The primary efficacy endpoint for this study is PFS, defined as the time from randomization to the first occurrence of disease progression, as determined by investigator tumor assessments using RECIST, or death on study from any cause. Death on study is defined as death from any cause within 30 days of the last dose of study drug prior to crossover. The first documented PD event prior to crossover in the control arm will be included in the analysis of the primary endpoint of PFS. | — |
Countries
Austria, Belgium, Germany, Hungary, Italy, Spain, United Kingdom
Outcome results
None listed