Early human epidermal growth factor receptor 2 (HER2) positive 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: - Age >= 18 years - Histologically confirmed invasive breast carcinoma - Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph node(s) at surgery after completion of neoadjuvant therapy - Diagnosis of HER2-positive breast cancer with assessment of hormone receptor and programmed death?ligand 1 status, as documented through central testing of a representative tumor tissue specimen - Completion of preoperative systemic chemotherapy and HER2-directed treatment - Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes - An interval of no more than 12 weeks between the date of primary surgery and the date of randomization - Eastern Cooperative Oncology Group Performance Status 0 or 1 - Screening left ventricular ejection fraction >= 50% on echocardiogram or multiple-gated acquisition scan after completion of neoadjuvant therapy and no decrease in left ventricular ejection fraction (LVEF) by more than 15% absolute points from the pre-chemotherapy LVEF. Alternatively, if the pre-chemotherapy LVEF was not assessed, the screening LVEF must be >= 55% after completion of neoadjuvant therapy - Life expectancy >= 6 months - Adequate hematologic and end organ function - For women of childbearing potential: agreement to remain abstinent or to use non-hormonal contraception, and agreement to refrain from donating eggs during the treatment period and for 7 months after the final dose of trastuzumab emtansine or trastuzumab - For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for 7 months after the final dose of trastuzumab emtansine or trastuzumab 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 1530 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 170
Exclusion criteria
Exclusion criteria: - Stage IV (metastatic) breast cancer; - Inadequate excision; - An overall response of disease progression according to the investigator at the conclusion of preoperative systemic therapy; - Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons; - History of other malignancy within 5 years prior to screening; - History of exposure to the following cumulative doses of anthracyclines: o Doxorubicin > 240 mg/m2; o Epirubicin or liposomal doxorubicin-hydrochloride (Myocet) > 480 mg/m2; o For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2; - Prior treatment with trastuzumab emtansine or atezolizumab; - Prior treatment with CD137 agonists or immune checkpoint blockade therapies; - Current Grade >= 2 peripheral neuropathy; - Dyspnea at rest; - Cardiopulmonary dysfunction; - Active or history of autoimmune disease or immune deficiency; - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis: o History of radiation pneumonitis in the radiation field is permitted; - Active tuberculosis; - Current severe, uncontrolled systemic disease; - Any known active liver disease; - Major surgical procedure, other than for breast cancer, within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the study; - Severe infection within 4 weeks prior to randomization; - Treatment with therapeutic antibiotics within 2 weeks (IV antibiotics) or 5 days (oral antibiotics) prior to randomization; - Prior allogeneic stem cell or solid organ transplantation; - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug and may affect the interpretation of the results, or may render the patient at high risk from treatment complications; - Treatment with a live, attenuated vaccine within 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab/placebo treatment or within 5 months after the final dose of atezolizumab/placebo; - Treatment with investigational therapy within 28 days prior to randomization; - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to randomization; - Treatment with systemic immunosuppressive medication within 2 weeks prior to randomization, or anticipation of need for systemic immunosuppressive medication during study treatment; - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins; - Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation; - History of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product; - Pregnant or breastfeeding, or intending to become pregnant during study treatment within 7 months after the final dose of trastuzumab emtansine or trastuzumab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine on the basis of invasive disease free survival (IDFS). ;Secondary Objective: - To evaluate the efficacy of atezolizumab when given in combination with with trastuzumab emtansine compared with placebo and trastuzumab emtansine on the basis of IDFS including second primary non breast invasive cancer, disease free survival, overall survival, distant recurrence-free interval, the proportion of patients in each arm with clinically meaningful deterioration in global health status/quality of life (GHS/QoL) assessed via the European Organisation for Research and Treatment of Cancer quality of life questionnaire for cancer, mean absolute scores and mean change from baseline scores in GHS/QoL, physical, role, cognitive function;- To evaluate safety of atezolizumab when given in combination with trastuzumab emtansine compared with placebo and trastuzumab emtansine; - To characterize pharmacokinetic profiles of atezolizumab and trastuzumab emtansine; - To evaluate immune response to atezolizumab and trastuzumab emtansine.;Primary end point(s): Invasive disease-free survival;Timepoint(s) of evaluation of this end point: Approximately 6 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Invasive disease-free survival including second primary non breast invasive cancer; 2. Disease-free survival; 3. Overall survival; 4. Distant recurrence-free interval; 5. The proportion of patients in each arm with clinically meaningful deterioration in GHS/QoL physical, role, and cognitive function as measured by scales of the European Organisation for Research and Treatment of Cancer quality of life questionnaire for cancer (EORTC QLQ C30); 6. Mean absolute scores and mean change from baseline scores in GHS/QoL, physical, role, and cognitive function, as assessed using the EORTC QLQ C30; 7. Incidence and severity of adverse events; 8. Maximum and minimum serum concentrations for atezolizumab and trastuzumab emtansine; 9. Incidence of antidrug antibodies (ADAs) to atezolizumab and to trastuzumab emtansine at specified timepoints.;Timepoint(s) of evaluation of this end point: 1-9. Approximately 6 years; for overall survival approximately 10 years from LPI. | — |
Countries
Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Poland, Portugal, Romania, Spain, United Kingdom
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed