breast cancer
Conditions
Interventions
Modified intervention after implementation of protocol amendment February 2017:
Trreatment with carboplatin/cyclofosfamide (group A) or paclitaxel (group C)
plus atezolizumab (groups B,D)
at progression:: paclitaxel plus atezolizumab
(group A) or carboplatin/cyclofosfamide plus atezolizumab (group C) or
treatment up to the invetigator (groups B,D).
Sponsors
BOOG Study Center
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histologically confirmed triple negative metastasized or locally advanced incurable breast cancer. See protocol section 5.2 for more details. - Histological confirmation of triple negative breast cancer of a metastatic lesion is recommended - Histological or cytological confirmation of metastatic breast cancer is required in case of normal CA 15.3 levels. Exception: see protocol section 5.2 for details. - Primary tumor or metastasis tissue sent to NKI-AVL for BRCA1-like testing - Pretreatment histological biopsy of a metastatic lesion for the translational research questions (tumor tissue from bone metastases cannot be used). Exception: see protocol section 5.2 for details. - No previous cytotoxic therapy for metastatic disease - Disease-free interval of at least 12 months after completion of (meo)adjuvant paclitaxel or (neo)adjuvant platinum compound - Disease-free interval of at least 6 months after completion of (neo)adjuvant docetaxel - Measurable or evaluable disease according to RECIST v1.1 - WHO performance status of 0 or 1
Exclusion criteria
Exclusion criteria: - Receptor conversion to hormone receptor positive (defined as >= 10% ER positive tumor cells) or HER2 positive - Other antitumor therapy within the previous 21 days, with the exception of endocrine therapy. The patient should have stopped any endocrine therapy before start study treatment. - Radiotherapy with palliative intent within the previous 7 days before start study medication (see protocol 5.3 for details) - Known CNS disease except for treated brain metastases (see protocol 5.3 for details) - Pre-existing peripheral neuropathy > grade 1 (NCI-CTC AE (version 4.03) at inclusion) - Use of denosumab is not allowed. See protocol section 5.3 for details. - Severe infection in the last 4 weeks. - Antibiotics in the last 2 weeks. - History of autoimmune disease. See protocol section 5.3 for details. - Prior allogeneic stem cell or solid organ transplantation - History of lung diseases such as idiopathic pulmonary fibrosis, pneumonitis. See protocol section 5.3 for more details - An infection requiring parenteral antibiotic - Positive test for hepatitis B, C HIV. See protocol section 5.3 for more details. - Active tuberculosis. - Live, attenuated vaccine within 4 weeks prior to randomization. - Prior treatment with anti cancer vaccins or immune checkpoint blockade therapies, including anti-CTLA-4, CD137 agonist, OX40 agonist, anti-PD-1, or anti-PD-L1 therapeutic antibodies - Treatment with systemic immunostimulatory agents, systemic corticosteroids or other systemic immunosuppressive medications. See protocol section 5.3 for details.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified primary variable after implementation of protocol amendment February 2017: Primary Outcome Measures (2x2 factorial design): Interaction test of BRCA1-like status vs. treatment (CC vs. Paclitaxel (both arms with or without atezolizumab). | — |
Secondary
| Measure | Time frame |
|---|---|
| Modified secondary variable after implementation of protocol amendment Sept 2024: Secondary Outcome Measures: • Evaluate whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide (PFS1). • Evaluate whether the addition of atezolizumab to paclitaxel is more favorable than adding atezolizumab to carboplatin-cyclophosphamide for patients with PD-L1 positive tumors defined as combined positive score (CPS) 10 or higher (PFS1). • PFS benefit of the addition of atezolizumab. • PD-L1 status and PFS • CD8 + TIL abundance and PFS • Moleculair subtypes and PFS • Predictive biomarkers for PFS gain. • PFS of the two first line chemotherapeutic regimens, regardless of bevacizumab yes or no. • Overall survival. • Adverse events. | — |
Countries
Netherlands
Outcome results
None listed