Study to Identify the Impact of Denosumab on the Immune System in Patients With HER2 Negative Breast Cancer

• Status: Withdrawn
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Female

Summary

The aim of this prospective, randomized, multicenter, open-label, explorative phase II study is to identify the impact of (neo)adjuvant denosumab on the systemic immunity and local immunologic microenvironment in postmenopausal patients with HER2 negative non-metastatic primary breast cancer.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Borstkanker Onderzoek Groep
• Collaborator: Amgen
• Treatments: Denosumab

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.