Effects of the inhibition of RANKL in pre-menopausal early breast cancer patients

Phase 1

Active, not recruiting

• Conditions: We have designed this study to investigate if denosumab can modulate a number of biological processes including prolferation, RANK signaling and the mammary stem cell subpopulation.; MedDRA version: 19.0Level: LLTClassification code 10006190Term: Breast cancer invasive NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-006224-21-BE
• Lead Sponsor: Jules Bordet Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-18
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Female
• Target Recruitment: 39

Inclusion Criteria

1) Female gender
2) Age = 18 years
3) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
4) Premenopausal status defined as the presence of active menstrual cycle or normal menses during the 6 weeks preceding the start of study treatment. Plasma levels of estradiol, FSH and LH are required to document phase of menstrual cycle. In women previously exposed to hysterectomy, or were using hormonal intrauterine device at the time of enrollment, premenopausal levels of estradiol, FSH and LH are required to be eligible
5) Non metastatic operable newly diagnosed primary invasive carcinoma of the breast that is:
a. Histologically confirmed
b. Primary tumor size greater than 1.5 cm, measured by any of clinical examination, mammography, ultrasound or magnetic resonance imaging
c. Any clinical nodal status
d. Fully operable and not fixed to chest wall.
6) Known HER2 status
7) Known estrogen receptor status (ER) and progesterone status (PgR)
8) Patient has adequate bone marrow and organ function as shown by:
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- Platelets = 100 x 109/L
- Hemoglobin (Hgb) = 9.0 g/dL
- Serum creatinine = 1.5 x ULN
- Total serum bilirubin = 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin = 3.0 x ULN, with direct bilirubin = 1.5 x ULN)
- AST and ALT = 1.5 x ULN
- Random blood sugar (RBS) = 200 mg/dL or = 11.1 mmol/L
- HbA1c = 8 %

9) Albumin-adjusted serum calcium = 8.0 mg/dL (= 2.0 mmol/L)
10) Women of childbearing potential must agree to use active local contraception method for the duration of the study and for at least 7 months after the last dose of study treatment
11) Patients are required to take calcium and vitamin D supplementation until the completion of the study treatment
12) Written informed consent form (ICF) for all study procedures according to local regulatory requirements prior to beginning of the study
13) Patients accept to make available tumor and normal tissue samples for submission to central laboratory at the Jules Bordet Institute, Brussels, Belgium, to conduct translational studies as part of this protocol.

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 39
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) History of any prior (ipsi and/or contralateral) breast cancer
2) Any clinical” T4 tumor defined by TNM including inflammatory breast cancer
3) History of non-breast malignancies within the 5 years prior to study entry (except carcinoma in situ of the cervix, of the colon, melanoma in situ and basal cell and squamous cell carcinomas of the skin)
4) Prior or planned systemic anti-cancer therapy before definitive surgery
5) Unhealed or planned dental/oral surgery, current or previous osteonecrosis or osteomyelitis of the jaw
6) Pregnant or lactating women or women of childbearing potential without a negative serum or urinary pregnancy test within 7 days prior to starting study treatment; irrespective of the method of contraception used
7) Active Hepatitis-B virus (HBV), Hepatitis-C virus (HCV) or human immunodeficiency virus (HIV) infection
8 )Known hypersensitivity to denosumab
9) Bilateral invasive tumors

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified