Explorative trial to identify the impact of denosumab on the systemic immunity and local immunologic microenvironment in postmenopausal patients with HER2 negative breast cancer.

Phase 2

Conditions: Breast cancer
mamma carcinoma
10006291

Registration Number: NL-OMON46766

Lead Sponsor: BOOG Study Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 75

Inclusion Criteria

• Postmenopausal, defined as 1 year without menstrual activity, previous bilateral oophorectomy, age older than 60 years or baselineFSH >20 U/l and estradiol <110 pmol/l.
• Clinical stage T1c + grade 3/4, stage II or III breast cancer amenable to adjuvant AC-T or ddAC-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>=3.0x10^9/l, neutrophils >=1.5 x 10^9/l, platelets >=100 x 10^9/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 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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change in intratumoral T-cell (CD4, CD8 and Treg) and Myeloid cell (M1/M2<br /><br>Macrophage, MDSC, DC) numbers and function between the baseline biopsy and the<br /><br>surgical specimen.</p><br>

Secondary Outcome Measures