Mamma carcinoma MedDRA version: 20.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Prolia
Pharmaceutical Form: Injection
INN or Proposed INN: Denosumab
CAS Number: 615258-40-7
Other descriptive name: DENOSUM
Sponsors
BOOG Study Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Postmenopausal, defined as 1 year without menstrual activity, previous bilateral oophorectomy, age older than 60 years or baseline FSH >20 U/l and estradiol 2.0 mmol/L (8.0mg/dL) • Accessible for treatment and follow-up • Written informed consent 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 37 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 38
Exclusion criteria
Exclusion criteria: • Evidence of distant metastases (M1) • History of invasive breast cancer • Prior chemotherapy or radiation therapy • Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix. • Serious other diseases as recent (last 6 months) myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias. • Prior or current bisphosphonate or denosumab usage. • Osteoporosis as demonstrated on dexa vfa scan, defined as T = 2.5 and/or a vertebral fracture. • Current active dental problems including dental abscess or infection of the jawbone (maxilla or mandible), non-healed dental or oral surgery, a current or prior diagnosis of osteonecrosis of the jaw or planned invasive dental procedures for the course of the study. • Known hypersensitivity reaction to any of the components of the treatment • Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the change in intratumoral T-cell (CD4, CD8 and Treg) and Myeloid cell (M1/M2 Macrophage, MDSC, DC) numbers and function between the baseline biopsy and the surgical specimen.; Secondary Objective: • PBMC before start treatment, at day of surgery and 7 days after last denosumab administration: o Determine the shift in T-cell (activated T effector cells and regulatory T cells) levels and function in PBMC samples. o Determine the change in mature and immature myeloid cells (M1, M2, MDSC, DC). o Determine the shift in myeloid cell function (IL-10 and IL-12 production after LPS or anti-CD40 triggering). o 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 denosumab administration: o 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 o Correlate tumor (biopsy and resection material), serum and PBMC immunologic parameters. • Toxicity according to NCI CTCAE v4.03. • Determine the descriptive difference in event-free survival (EFS) at 3 year based on immune response. ;Primary end point(s): Change in intratumoral T-cell (CD4, CD8 and Treg) and Myeloid cell (M1/M2 Macrophage, MDSC, DC) numbers and function between the baseline biopsy and the surgical specimen.;Timepoint(s) of evaluation of this end point: At time of operation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • PBMC before start treatment (t=1), at day of surgery before surgery (t=2) and 7 days after last denosumab administration (t=3): o Shift in activated T effector cell levels (Ki67, HLA-DR, CD45RO, CD25, CD69, PD-1, TIM-3 and NKG-2A); o Shift in regulatory T-cell levels (CD3, CD4, CD25, CD127, CD45RA, Foxp3, helios, CTLA-4 and Ki67); o Change in functional response of T-cells (stimulation with recall antigens). o Change in mature and immature myeloid cells (M1, M2,MDSC, DC). o Shift in myeloid cell function (IL-10 and IL-12 production after LPS or anti-CD40 triggering). o Change in stimulation capacity APCs (MLR + cytokine production after restimulation). • Serum before start treatment (t=1), at day of surgery before surgery (t=2) and 7 days after last denosumab administration (t=3): o Change in serum levels for RANKL, OPG by ELISA; TNF-alpha, IL-1-beta, IL-6, IL-7,IL-10, IL-15, IL-12, IFN gamma by luminex. • Tumor: o Correlation of tumor (biopsy and resection material) (intratumoral T-cell and Myeloid cell numbers), serum cytokine levels and PBMC immunologic parameters. • Toxicity according to NCI CTCAE v4.03. • Difference in descriptive event-free survival (EFS) at 3 year based on immune response. ; Timepoint(s) of evaluation of this end point: • Before start treatment (t=1), at day of surgery before surgery (t=2) and 7 days after last denosumab administration (t=3) • Before start treatment (t=1), at day of surgery before surgery (t=2) and 7 days after last denosumab administration (t=3) • Tumor: baseline and surgery. Serum/PBMC: t=1, t=2, t=3 • From start till end of therapy + until 30 days after completion of the therapy. • At 3 years after randomization | — |
Countries
Netherlands
Contacts
Public ContactDr. J.R. Kroep
Leiden University Medical Center
Outcome results
None listed