A Multinational, Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Trial to Investigate Safety and Efficacy of Tibolone (Org OD14) in Women With Climacteric Symptoms and a History of Breast Cancer
A growing proportion of women diagnosed with early stage breast cancer seek help with
vasomotor and sexual complaints. Frequently, these symptoms result from adjuvant cancer
treatment, irrespectively whether this is hormonal (e.g. tamoxifen, aromatase inhibitors),
cytotoxic, or surgical (oophorectomy) in nature. Estrogen-containing hormone therapy is
effective, but considered unsafe. Non-hormonal therapy is less effective. Tibolone, which
does not increase mammographic breast density, has proven to be effective and thus could be
an important treatment option for women persistently seeking help.
The objective of this trial is to demonstrate safety, efficacy and tolerability of oral 2.5
mg tibolone daily in breast cancer patients, who, after surgery, have no evidence of disease
and who suffer from climacteric complaints. Primary study endpoint is breast cancer
recurrence, including primary contralateral breast cancer. Secondary outcome variables
include menopausal symptoms, bone mineral density and health-related quality of life.
Patients were eligible for this study when they had been surgically treated within the
previous 5 years for histologically confirmed T1-3, N0-2, M0 breast cancer and had to have
vasomotor symptoms, with a last menstruation at least 12 months before (or bilateral
The LIBERATE Trial has been designed to show non-inferiority of tibolone compared to
placebo. Adequate sample size was estimated to be at least 1500 subjects in each arm,
assuming a breast cancer recurrence rate of 5% per year in the first 3 years and an dropout
rate of 5% per year.
The LIBERATE Study has successfully included the appropriate number of women with the proper
risk profile so that significant results can be obtained in relation to safety and efficacy
of tibolone in breast cancer patients with menopausal complaints.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
To show non-inferiority in breast cancer recurrence of tibolone 2.5 mg versus placebo in women with climacteric symptoms who have been surgically treated for primary breast cancer within the last 5 years
At clinical completion
Australia: National Health and Medical Research Council