HER2-positive early breast cancer
Conditions
Interventions
Trade Name: Tecentriq
Product Name: Atezolizumab
Product Code: RO5541267/F03
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
CAS Number: 1380723-44-3
Other
Sponsors
ABCSG (Austrian Breast & Colorectal Cancer Study Group)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient / Disease Specifics (1) Signed informed consent obtained prior to any study specific assessments and procedures which are not performed as part of standard of care (2) Female patients, age = 18 years at the time of signing informed consent form (ICF) (3) Histologically confirmed invasive, unilateral adenocarcinoma of the breast with the following characteristics: - cT1c-4a-d, N0–3, M0 per AJCC (American Joint Committee on Cancer) Breast Cancer Staging version 8 - In the case of a multifocal tumor (defined as the presence of two or more foci of cancer within the same breast quadrant), the largest lesion must be > 1 cm and designated as the “target” lesion for all subsequent tumor evaluations - In the case of a multicentric tumor (defined as the presence of two or more foci of cancer within different quadrants), the largest lesion must be > 1 cm and designated as the “target” lesion for all subsequent tumor evaluations - histologically confirmed HER2 positivity; HER2 measurement to be assessed locally as 3+ by immunohistochemistry or 2+ by immunohistochemistry with HER2 amplification by In Situ Hybridization (ISH) according to the ASCO/CAP guideline - If biopsies were taken from more than one focus, all histologically confirmed invasive breast cancer foci have to be HER2 positive. In case of a multicentric tumor, at least two foci in different breast quadrants have to be histologically confirmed HER2 positive breast cancer - Hormone receptor positive or negative tumors (4) Tumor tissue from FFPE core-needly biopsy of breast tumor measuring at least 3x1 mm must be transmitted to a central sample repository and feedback on central TIL assessment must be available prior to randomization (5) Neoadjuvant chemotherapy indicated (at the discretion of the investigator) (6) ECOG performance status 0-1 (7) In women of childbearing potential, urine or serum pregnancy test must be negative within 28 days prior to randomization. In postmenopausal women or hysterectomized patients, pregnancy tests do not need to be performed (8) Adequate left ventricular ejection fraction (LVEF) at baseline, defined as LVEF = 55 % by either echocardiogram or MUGA Baseline body function specifics (9) ANC = 1.5 x 10^9/L (1500/µL) without granulocyte colony-stimulating factor support (10) Lymphocyte count = 0.5 x 10^9/L (500/µL) (11) Platelet count = 100 x 10^9/L (100,000/µL) without transfusion (12) Hemoglobin = 90 g/L (9 g/dL). Patients may be transfused to meet this criterion (13) For patients not receiving therapeutic anticoagulation: INR or aPTT = 1.5 x ULN. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen. (14) Aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) = 2.5 x ULN (15) Serum bilirubin =1.5 x ULN with the following exception: Patients with known Gilbert’s syndrome: serum bilirubin level = 3 x ULN (16) Serum creatinine = 1.5 x ULN AND creatinine clearance = 50 mL/min (calculated using the Cockcroft-Gault formula) (17) Ability to understand and fill out PRO questionnaires 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 29 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: (1) Metastatic or locally advanced disease (without loco-regional treatment options with curative intention) (2) Patient receiving any prior cancer therapy for invasive breast cancer and/or the same disease (3) Bilateral invasive breast cancer (4) Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways (5) History of other malignancy; patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible (6) Pregnant or lactating women (7) Serious medical or psychiatric disorders that would interfere with the patient’s safety or informed consent (at the discretion of the investigator) (8) Clinically significant cardiovascular disease, requiring medication during the study and which might interfere with regularity of the study treatment, or not controlled by medication (at the discretion of the investigator) (9) Clinically relevant, active bacterial, viral or fungal infection (at the discretion of the investigator) (10) History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, uncontrolled inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible as well (11) Prior allogeneic stem cell or solid organ transplantation (12) Concurrent participation in another clinical trial with the same primary endpoint and/or concurrent participation in another clinical trial with an investigational product (13) Known hypersensitivity to the study drugs (14) Active tuberculosis (15) Patients receiving live, attenuated vaccine within 4 weeks prior to Cycle 1 Day 1 (= V1) AND not fit for study participation as per investigator’s assessment. (16) Treatment with therapeutic oral or iv antibiotics within 2 weeks prior to randomization (17) Known uncontrolled HIV, HCV and HBV infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of a neoadjuvant immunochemotherapy regimen consisting of atezolizumab, trastuzumab, pertuzumab and epirubicin in regards to pathologic complete response (pCR = ypT0/is, ypN0) which is assessed in the overall study population at the time of surgery;Secondary Objective: To evaluate efficacy in regards to - Residual Cancer Burden (RCB) - Overall Response Rate (ORR) which are assessed in the overall study population at the time of surgery;Primary end point(s): Proportion of patients with a pCR (=ypT0/is, ypN0) assessed in the overall study population;Timepoint(s) of evaluation of this end point: Surgery | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Two variables of treatment efficacy assessed in the overall study population - Proportion of patients with RCB 0, RCB I, RCB II and RCB III - Proportion of patients with ORR according to modified RECIST;Timepoint(s) of evaluation of this end point: Surgery | — |
Countries
Austria
Contacts
Public ContactTrial Office
ABCSG (Austrian Breast & Colorectal Cancer Study Group)
Outcome results
None listed