A randomised, double-blind, placebo controlled trial to examine the effects of total oestradiol depletion on bone microstructure and the efficacy of denosumab in preventing microstructural bone decay in premenopausal women with early breast cancer
Efficacy study to evaluate denosumab compared to placebo in preventing microstructural bone decay in premenopausal women receiving total oestradiol depletion therapy for early breast cancer
Professor Mathis Grossmann
114 participants
Sep 8, 2016
Interventional
Conditions
Summary
The primary purpose of this study is to compare the efficacy of denosumab treatment with placebo in preventing bone decay in premenopausal women being treated with ovarian suppression and aromatase inhibition for breast cancer. Who is it for? You may be eligible to enrol in this trial if you are a premenopausal woman aged 18 to 55 who has been diagnosed with oestrogen-receptor positive, non-metastatic breast cancer (TxNxM0) for which you are scheduled to begin ovarian suppression and aromatase inhibition therapy which is intended to last for at least 12 months. Study details All participants enrolled in this trial will be randomly allocated (by chance) to receive either denosumab once every 6 months by subcutaneous injection or to receive placebo once every 6 months for a 12-month study period. Participants will be followed-up at 6 and 12 months after starting the trial drug/placebo with scans, blood tests and questionnaires which will be used to measure bone density and structure, body composition, blood markers of bone health and cardiovascular risk and quality of life. It is hoped that the findings from this trial will provide information on the extent of bone decay which occurs as a result of ovarian suppression and aromatase inhibition therapy, and the efficacy of denosumab in preventing this decay in premenopausal women with oestrogen-receptor positive breast cancer.
Eligibility
Inclusion Criteria9
- Premenopausal women with oestrogen-receptor positive, non-metastatic breast cancer (TxNxM0) based on documented pathological and radiological evaluation. Menopausal status will be defined clinically at the diagnosis of breast cancer.
- Premenopausal: a regular cycle in the last 3 months prior to diagnosis of breast cancer
- Perimenopausal: absent cycles for 3-12 months
- Postmenopausal: absent cycles for 12 months or more
- About to commence treatment with ovarian suppression with a view to subsequent aromatase inhibition as determined by the treating oncologist
- Endocrine therapy intended for at least 12 months
- Eastern Cooperative Oncology Group (ECOG) 0 and 1
- Able to personally read and understand the Participant Information and Consent Form and provide written, signed and dated informed consent to participate in the study
- Able and willing to meet all protocol-required procedures and visits
Exclusion Criteria20
- Bone mineral density T-score at the lumbar spine/hip/femoral neck <-2.0SD
- Pre-existing minimal trauma fractures (excluding fractures of fingers, toes, hands, feet and skull)
- Current evidence or prior history of any of the following:
- Metabolic bone disorder(s)
- Drugs for treatment of bone-related disorders
- Prolonged glucocorticoid use for 2 or more weeks continuously in the past 6 months
- Significant inflammatory or malabsorptive condition(s)
- Osteonecrosis or osteomyelitis of the jaw
- Atypical femoral fracture(s)
- Diabetes mellitus
- History of any solid organ or bone marrow transplant
- Malignancy within the last 5 years (except breast cancer and non-melanoma skin cancers)
- Abnormalities of the following per central laboratory reference ranges:
- Hypo/hypercalcaemia
- Hypo/hyperparathyroidism
- Renal impairment (eGFR <45ml/min/1.73m2)
- -hydroxy vitamin D deficiency (<12nmol/L). Repletion will be allowed and participants may be re-screened.
- Self-reported recreational drug use or alcohol dependence within 12 months prior to screening
- Pregnancy
- History or evidence of any other clinically significant disorder, condition or disease that in the opinion of the study investigator would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
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Interventions
Denosumab 60mg subcutaneous injection at 6-month intervals for a 12-month study duration administered by trial investigator.
Locations(1)
View Full Details on ANZCTR
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ACTRN12616001051437