ER negative, PR negative and HER2 negative (triple negative) breast cancer MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: Carboplatin
Pharmaceut
Sponsors
palleos healthcare GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Female and male patients, age at diagnosis 18 years and above ? Written informed consent prior to admission to this study ? Histologically confirmed unilateral primary invasive carcinoma of the breast ? Clinical T1c – T4d * ? Stage N0 - N3 until 21 patients (5%) with stage N3 are randomized, thereafter N0 - N2 ? TNBC defined by and confirmed by central pathology: o ER negative ( 1 x ULN to 1.5 x ULN due to Gilbert’s disease or similar syndrome involving slow conjugation of bilirubin o ALK must be = 2.5 x ULN for the lab o AST and ALT must be =1.5 x ULN for the lab. o Patients with AST and ALT or ALK > 1 x ULN are eligible for inclusion if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 3 months prior to randomization (and part of SOC) does not demonstrate metastatic disease and the requirements in criterion (just above) are met o Patients with ALK that is > 1 x ULN but less than or equal to 2.5 x ULN or with unexplained bone pain are eligible if bone imaging does not demonstrate metastatic disease. o Creatinine clearance = 40ml/min performed 28 days prior to screening *TNM staging according to the Union for International Cancer Control (UICC) classification 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 412 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: ? Previous history of malign diseases, non-melanoma skin cancer and carcinoma of the cervix are allowed if treated with curative intent ? Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of Paclitaxel, Carboplatin, Epirubicin, Cyclophosphamide or Atezolizumab ? Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol ? Concurrent treatment with other drugs that are contraindicating the use of the study drugs ? Existing pregnancy ? Breastfeeding ? Sequential breast cancer ? Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project (except registry study) within 30 days prior to study entry ? Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to: o Uncompensated chronic heart failure or systolic dysfunction (LVEF 180 mmHg or diastolic > 100 mmHg). ? Inadequate organ function including but not confined to: o hepatic impairment as defined by bilirubin > 1.5 x ULN o pulmonary disease (severe dyspnea at rest requiring oxygen therapy) ? Abnormal blood values: o Platelet count below 100,000/mm3 o AST/ALT > 1.5 x ULN o Hypokalaemia > CTCAE grade 1 o Neutropenia > CTCAE grade 1 o Anaemia > CTCAE grade 1 ? Administration of a live, attenuated vaccine within 4 weeks before cycle 1 day 1 or anticipation that such a vaccine will be required during the study ? Treatment with systemic immunosuppressive medications (including but not limited to interferons, IL-2) within 28 days or 5 half-lives of the drug, whichever is longer, prior to randomization ? Treatment with systemic immunosuppressive medications (including but not limited to Prednisone, Cyclophosphamide, Azathioprine, Methotrexate, Thalidomide, and anti-TNF factor agents) within 14 days prior to screening or anticipation of need for systemic immunosuppressive medications during the study ? Patients with prior allogeneic stem cell or solid organ transplantation ? Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions: o Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study. o Patients with controlled Type 1 diabetes mellitus on a stable dose of insulin regimen may be eligible for this study. o Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are permitted
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare efficacy in terms of pCR in TNBC with Atezolizumab 2-week monotherapy window followed by neoadjuvant CTX with Atezolizumab (Arm A) to neoadjuvant CTX with Atezolizumab (Arm B).;Secondary Objective: 1. Asses and compare safety of Atezolizumab monotherapy window of 2 weeks followed by neoadjuvant treatment with Atezolizumab in combination with CTX (Arm A) to neoadjuvant CTX with Atezolizumab (Arm B): - of patients with an ER/PR expression of <1% and an ER/PR expression of 1% to 10%. - per alternative pCR definitions 2. Compare early biological response as measured by Complete Cell Cycle Arrest (CCCA), decrease of Ki-67 expression (=30%), low cellularity and TILs (=60%), or a combined early response 3. Compare early biological response as measured by CCCA, decrease of Ki-67 expression (=30%), low cellularity and TILs (=60%), or a combined early response 4. Assess and compare the prognostic and predictive values of the biomarkers 5.Compare the efficacy of Atezolizumab mono-therapy window of 2 weeks followed by treatment in (Arm A) to the treatment according (Arm B): - by disease free survival (DFS) - by overall survival (OS) - by event free survival (EFS);Primary end point(s): a) pCR defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0) ;Timepoint(s) of evaluation of this end point: After 26 weeks in Arm A and after 24 weeks in Arm B. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1. constantly, on occurrence 2. - 5. 4 efficacy interim analyses in blocks of 40 patients after 100, 140, 180 and 220 patients 6. - 12. after 14/28 days (+/- 2 days) of treatment 13. defined as time from the first date of no disease or death 14. from randomization to death 15. after randomization till death;Secondary end point(s): b) Safety (incidence, relationship, seriousness, and severity of all AEs, SAEs, AESIs coded by medical dictionary for regulatory activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to common terminology criteria of adverse events (CTCAE) V5.0) c) pCR defined as no residual invasive tumor cells in the breast and in the lymph nodes (ypT0/is, ypN0) in patients with an ER/PR expression of < 1% and an ER/PR expression of 1% to 10% d) pCR defined as no tumor cells (invasive or non-invasive) in the breast but also in the lymph nodes (ypN0, ypT0) e) Near pCR defined as residual tumor < 5 mm in the breast irrespective of in situ and lymph nodes status f) pCR defined as no invasive tumor in the breast, irrespective of lymph node status g) Decrease of Ki-67 expression versus baseline after 14/28 days (+/- 2 days) of treatment as continuous predictor h) TILs after 14/28 days (+/- 2 days) of treatment as continuous predictor i) CCCA: Ki-67 expression = 2.7% after 14/28 days (+/- 2 days) of treatment j) Low cellularity: < 500 tumor cells after 14/28 days (+/- 2 days) of treatment k) Decrease of Ki-67 expression versus baseline by 30% or more after 14/28 days (+/- 2 days) of treatment l) TILs = 60% after 14/28 days (+/- 2 days) of treatment m) Combined early response defined by o CCCA (Ki-67 expression < 2.7%) or o low cellularity or o decrease of Ki-67 expression (versus baseline) by 30% or more or o TILs = 60% n) DFS1 defined as time from the first date of no disease [i.e. date of surgery] to the first occurrence of disease recurrence or death from any cause o) OS | — |
Countries
Germany
Contacts
Public ContactClinical Trials Information
palleos healthcare GmbH
Outcome results
None listed