Comparison of neoadjuvant chemotherapy with PDL1-inhibition (Atezolizumab) and Atezolizumab two-week window to chemotherapy with PDL1-inhibition (Atezolizumab) and identifying biomarkers predicting (early) response to or resistance against Atezolizumab (alone and with CTX) allowing patients stratification in future clinical trials
- Conditions
- ER negative, PR negative and HER2 negative (triple negative) breast cancerMedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001651-40-DE
- Lead Sponsor
- palleos healthcare GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 458
? 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 (< 10% positive cells in IHC) and PR negative (< 10% positive cells on IHC)
o HER2 negative breast cancer:
? Either defined by IHC: ICH scores of 0 - 1 or an ICH score of 2 in combination with a negative ISH
? Or defined by ISH: negative ISH
? Identifiable PD-L1 IC-status by central pathology (positive or negative) by means of VENTANA PD-L1 (SP142) assay; positive status is defined by PD-L1 expression on IC on = 1% of the tumor area, negative status is defined by PD-L1 expression on IC on < 1% of the tumor area
? No clinical evidence for distant metastasis (cM0)
? Tumor block available for translational research
? Performance Status ECOG = 1 or KI = 80%
? Negative pregnancy test (urine or serum) within 7 days prior to screening in premenopausal patients
? Women of childbearing potential and male patients with partners of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) including at least one non-hormonal contraceptive measures during the study treatment and for 5 months following the last dose of study treatment such as:
o IUD
o bilateral tubal occlusion
o vasectomized partner
o sexual abstinence
? The patient must be accessible for treatment and follow-up
? Normal cardiac function:
o Normal ECG (within 6 weeks prior to screening)
o Normal LVEF on ECG
? Normal thyroid function
o Normal TSH and FT4
? Blood counts within 14 days prior screening:
o absolute neutrophile count (ANC) must be = 1,500/mm3
o Platelet count must be = 100,000/mm3
o Hemoglobin must be = 10 g/dl
? Hepatic functions:
o Total bilirubin must be = 1 upper limit of normal (ULN) for the lab unless the patient has a bilirubin elevation > 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
? 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 < 55%, CHF NYHA classes II-IV),
o unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate = 100 bpm at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block,
o Angina pectoris within the last 6 months requiring anti-anginal medication,
o Clinically significant valvular heart disease,
o Evidence of myocardial infarction on ECG,
o Poorly controlled hypertension (e.g., systolic > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method