Patients with operable HER2-positive primary breast cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Adult patients. >/= 18 years of age - Non-metastatic primary invasive HER2-positive carcinoma of the breast that is adequately excised, and that is either node-positive (except T0), or node-negative but with presence of at least one risk factor as defined by the protocol (the latter option only applies to protocol version A. Node-negative patients are NOT allowable under protocol version B.) - Eastern Cooperative Oncology Group (ECOG) performance status /= 55% - Women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception (as defined by the protocol) by the patient and/or partner for the duration of the study treatment and for at least 7 months after the last dose of study drug 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 4080 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 720
Exclusion criteria
Exclusion criteria: - History of any prior (ipsi- and/or contralateral) invasive breast cancer - History of non-breast malignancies within the 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinomas of the skin - Any "clinical" T4 tumor as defined by TNM, including inflammatory breast cancer - Any previous systemic chemotherapy for cancer or radiotherapy for cancer - Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy for cancer - Concurrent anti-cancer treatment in another investigational trial - Serious cardiac or cardiovascular disease or condition - Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare invasive disease-free survival (IDFS) in patients with HER2-positive breast cancer randomized to chemotherapy plus one year of trastuzumab plus placebo or chemotherapy plus one year of trastuzumab plus pertuzumab.;Secondary Objective: To compare invasive disease-free survival including second non-breast cancers, disease-free survival (DFS), overall survival (OS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), cardiac safety, overall safety and health-related quality of life (HRQL) in the two treatment arms.;Primary end point(s): The primary endpoint of the trial is Invasive Disease-Free Survival (IDFS). It is a composite endpoint which is defined as the time from randomization until the date of the first occurrence of one of the following events: • Ipsilateral invasive breast tumor recurrence (ie, an invasive breast cancer involving the same breast parenchyma as the original primary lesion); • Ipsilateral local-regional invasive breast cancer recurrence (ie, an invasive breast cancer in the axilla, regional lymph nodes, chest wall and/or skin of the ipsilateral breast); • Distant recurrence (ie, evidence of breast cancer in any anatomic site – other than the two abovementioned sites – that has either been histologically confirmed or clinically diagnosed as recurrent invasive breast cancer); • Contralateral invasive breast cancer; • Death attributable to any cause including breast cancer, non-breast cancer or unknown cause (but cause of death should be specified if at all possible).;Timepoint(s) of evaluation of this end point: The final analysis will take place when approximately 379 IDFS events have occurred. In order to ensure sufficient data maturity (particularly in patients enrolled after the protocol amendment B), in the event that 379 IDFS events are reached sooner than 30 months after last patient enrolled (as is anticipated based on the revised IDFS assumptions), the primary analysis will be delayed unti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints of the present trial include OS (overall survival), DFS (disease-free survival), IDFS (invasive disease-free survival) including second primary non-breast cancer, RFI (recurrence-free interval) and DRFI (distant recurrence-free interval). Additionally, cardiac and overall safety, as well as quality of life will be evaluated.;Timepoint(s) of evaluation of this end point: Secondary variables will be analyzed in a similar manner as the primary endpoint to compare the two treatment arms, estimate 3-year event rates (5-year event rates for OS). An event driven OS analysis is planned when 640 deaths have occurred, estimated to be around nine and a half years after last patient randomized. Assuming the primary analysis for IDFS occurs after 379 events then the first interim OS analysis will be made available at this time (estimated to be 4 to 5 years after the first patient is randomized). Two subsequent interim analyses of OS will be performed approximately 2.5 and 5 years later, with the final event-driven OS analysis defined above. | — |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czech Republic, Denmark, El Salvador, European Union, France, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Panama, Peru, Philippines, Russian Federation, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd.
Outcome results
None listed