Women with a diagnosis of invasive unilateral, early high-risk and locally advanced or inflammatory, triple negative (HER2-negative and ER-negative and PgRnegative) breast cancer of high proliferation or grade suitable for neoadjuvant Therapy. MedDRA version: 20.0 Level: PT Classification code 10006200 Term: Breast cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10006196 Term:
Conditions
Interventions
Product Name: Atezolizumab
Product Code: MPDL3280A
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: MPDL3280A
Concentration unit: mg/m
Sponsors
Fondazione Michelangelo - Avanzamento dello studio e cura dei tumori
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female patients aged 18 years or older with early high-risk (T1cN1 ; T2N1; T3N0) or locally advanced and inflammatory breast cancers (stage III A-C according to AJCC) suitable for neoadjuvant treatment 2. Histologically confirmed unilateral breast cancer with invasive ductal histology not otherwise specified (NOS) of high proliferation or grade 3. HER2 negative disease defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either In Situ Hybridization (ISH) or other amplification tests done locally. 4. Negative estrogen receptor (ER) and progesterone receptor (PgR), both =65 years) yes F.1.3.1 Number of subjects for this age range 272
Exclusion criteria
Exclusion criteria: 1.Evidence of bilateral breast cancer or metastatic disease (M1) 2.Cases with an histology different from invasive ductal NOS of high proliferation or grade 3.Patients with HER2-positive disease according to ASCO/CAP guidelines 2013 are considered not eligible for the study 4.Pregnant or lactating women. 5.Previous treatment with chemotherapy, hormonal therapy or an investigational drug for any type of malignancy. Presence of bleeding tumors 6.Previous investigational treatment for any condition within 4 weeks or five half-lives of randomization date, whichever is longer 7.Administration of a live,attenuated vaccine within 4 weeks before C1D1 or anticipation that such a live attenuated vaccine will be required during study or within 5 months after last atezolizumab dose. 8.Previous or concomitant invasive malignancy of any other type or previous invasive breast cancer or curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally eligible 9.Pre-existing motor or sensory neuropathy of grade > 1 for any reason 10.History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion Proteins, to human albumin solution, hypersensitivity to platinum containing compounds. 11.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab formulation 12.Patients with prior allogeneic stem cell or solid organ transplantation 13.History of autoimmune disease including, but not limited to, systemic lupus erythematosus, heumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Bell’s palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis 14.History of idiopathic pulmonary fibrosis (including bronchiolitis obliterans with organizing pneumonia) or evidence of active pneumonitis on screening chest computed tomography scan 15.Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease 16.History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. All patients have to undergo hepatitis and HIV testing during screening. 17.Active tuberculosis 18.Severe infections within 4 weeks prior to C1D1, including, but not limited to, ospitalization for complications of infection, bacteremia, or severe pneumonia. Signs or symptoms of significant infection within 2 weeks prior to cycle 1 Day 1 19.Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1 20.History of documented congestive cardiac failure; New York Heart Association (NYHA) Class II or greater CHF; angina pectoris requiring anti-anginal medication or unstable angina within 6 months prior to cycle 1 Day 1; evidence of transmural infarction on ECG; myocardial infarction stroke or transient ischemic attack (TIA) within 6 months prior to cycle 1 Day 1; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias 21.Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare Event Free Survival (EFS) in the 2 study arms from the time of randomization;Secondary Objective: - Compare the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery - Compare clinical overall response (cOR) at the end of neo-adjuvant therapy. - Compare Distant EFS (DEFS) from the time of randomization - Compare overall survival from the time of randomization - Evaluate tolerability of the treatment regimens in the different study arms - Conduct molecular and clinical analyses to assess the presence of prognostic and/or predictive markers of benefit and/or resistance to the study regimens and to improve our understanding of breast cancer disease.;Primary end point(s): Event Free Survival (EFS);Timepoint(s) of evaluation of this end point: time from randomization to the first date of disease progression while on primary therapy or disease recurrence (local, regional, distant, invasive contralateral breast) after surgery or death due to any cause. (before surgery and every 12 months after surgery (until EOS = 5 years after last patient in) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 Pathological Complete Response (pCR) 2 Relationship between pCR and EFS 3 Clinical Overall Response (cOR) at the end of neo-adjuvant treatment 4 Distant Event Free Survival 5 Overall Survival 6 Safety;Timepoint(s) of evaluation of this end point: 1 at time of surgery 2 at EOS 3 at the end of neo-adjuvant treatment 4 before surgery and every 12 months after surgery (until EOS = 5 years after last patient in) 5 time from randomisation to death 6 time form treatment start until end of treatment | — |
Countries
Austria, France, Germany, Ireland, Italy, Poland, Russian Federation, Singapore, Spain, Taiwan
Contacts
Public ContactUfficio Operativo
Fondazione Michelangelo
Outcome results
None listed