Explorative trial to identify the impact of DENOsumab on the systemic immunity and local immunologic microenvironment in postmenopausal patiënts with HER2 negative breast cancer
Indication
Adjuvant
Subindication
HER2-, any HR
Target sample size
75
Estimated study completion date
01/10/2022
Contact
Sponsor
BOOG
Principal Investigator(s)
Dr. J.R. Kroep (Leids Universitair Medisch Centrum)
Study manager
Drs. A.F. de Groot, LUMC (studiecoördinator) T. Volker, MSc, BOOG Study Center (Project medewerker) Dr. A. E. van Leeuwen-Stok, BOOG Study Center (Clinical Study Manager)
Please note that the PERIDENO study will not be continued. Coordinating investigator/project leader: A.F. de Groot (Leids Universitair Medisch Centrum)
Objectives
Primary objective: Determine the change in intratumoral T-cell (CD4, CD8 and Treg) and Myeloid cell (M1/M2 Macrophage, MDSC, DC cell) numbers and function between the baseline biopsy and the surgical specimen. Secondary objectives: PBMC before start treatment, at day of surgery and 7 days after last chemotherapy administration: Determine the shift in T-cell (activated T effector cells and regulatory T cells) levels and function in PBMC samples. Determine the change in mature and immature myeloid cells (M1, M2, MDSC, DC). Determine the shift in myeloid cell function (IL-10 and IL-12 production after LPS or anti-CD40 triggering). Determine the change in stimulation capacity APCs (MLR + cytokine production after restimulation). Serum before start treatment, at day of surgery and 7 days after last chemotherapy administration): Determine the change in RANKL, OPG by ELISA; TNF-alpha, IL-1-beta, IL-6, IL-7, IL-10, IL-15, IL-12, IFN gamma by luminex. Tumor Correlate tumor (biopsy and resection material), serum and PBMC immunologic parameters. Toxicity according to NCI CTCAE v4.03. Determine the descriptive difference in disease free survival (DFS) at 3 year based on immune response.