Study to Identify the Impact of Denosumab on the Immune System in Patients With HER2 Negative Breast Cancer (PERIDENO)
Breast Neoplasms
About this trial
This is an interventional basic science trial for Breast Neoplasms focused on measuring Breast cancer, Denosumab, Chemotherapy, Immunity, Immune system, PERIDENO
Eligibility 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 <110 pmol/l.
- Clinical stage T1c + grade 3, stage II or III breast cancer amenable to adjuvant AC-T combination chemotherapy.
- Measurable disease (breast and/or lymph nodes).
- Histological proven HER2-negative breast cancer in the core biopsy material.
- WHO 0-2.
- Adequate bone marrow function (within 4 weeks prior to randomization): WBC≥3.0x109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l.
- Adequate liver function (within 4 weeks prior to randomization): bilirubin ≤1.5 X upper limit of normal (UNL) range, ALAT and/or ASAT ≤2.5 x UNL, Alkaline Phosphatase ≤5 x UNL.
- Adequate renal function (within 4 weeks prior to randomization): the calculated creatinine clearance should be ≥50 ml/min.
- Albumin-adjusted serum calcium > 2.0 mmol/L (8.0mg/dL)
- Accessible for treatment and follow-up.
- Written informed consent.
Exclusion Criteria:
- Evidence of distant metastases (M1).
- History of 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.
- Prior or current bisphosphonate or denosumab usage.
- Serious other diseases as recent (last 6 months) myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias.
- 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.
Sites / Locations
- Ziekenhuisgroep Twente (Twenteborg ZH Almelo)
- Gelre ziekenhuizen
- Zuyderland Medisch Centrum (Heerlen)
- Spaarne Gasthuis (Hoofddorp)
- Leiden University Medical Center
- Fransiscus (Vlietland)
- VieCuri Medisch Centrum (Venlo)
- 't Lange Land Ziekenhuis
Arms of the Study
Arm 1
Arm 2
Arm 3
No Intervention
Experimental
Experimental
No denosumab
Denosumab 120 mg
Denosumab 60 mg
All patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are not additionally treated with denosumab.
All patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are additionally treated with denosumab 120 mg every 3 weeks. First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.
All patients undergo surgery followed by adjuvant chemotherapy. Patients in this study arm are additionally treated with denosumab 60 mg every 6 months. First denosumab gift is before surgery, last denosumab gift is together with the last cycle of chemotherapy.