Clinical trial NCT00408863 (phase 3, status: completed)
Conditions: breast cancer, climacteric symptoms
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: tibolone, placebo
SMILES: [H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC(=O)CC3)C[C@@]([H])(C)[C@@]21[H], CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed and surgically treated invasive breast carcinoma (T1/2/3
             N0/1/2 M0), irrespective of hormonal (estrogen/progestogen) receptor status.

          -  Last menstrual bleeding at least 12 months before the start of the study or
             ovariectomized or hysterectomized or currently being treated with gonadotropin
             releasing hormone analogs.

          -  Vasomotor symptoms whether related to natural menopause, ovariectomy, or to breast
             cancer therapy (chemotherapy, tamoxifen, aromatase inhibitors or other anticancer
             therapy).

          -  In subjects with an intact uterus, a 'normal' endometrium, defined as:

               1. in tamoxifen users: absence of endometrial polyps

               2. in non-tamoxifen users: double layer endometrial thickness <=4 mm as assessed by
                  TVUS or double layer endometrial thickness >4 mm and <=8 mm as assessed by TVUS
                  plus an endometrial biopsy result of inactive/atrophic.

          -  Voluntary written informed consent and willing and able to make reasonable efforts to
             meet all clinical trial requirements.

        Exclusion Criteria:

          -  Age >75 years at baseline.

          -  Ductal carcinoma in situ (DCIS) of the breast without the existence of invasive breast
             carcinoma.

          -  Invasive breast carcinoma having a tumor of any size with direct extension to chest
             wall or skin (T4) and/or having metastasis to ipsilateral mammary lymph node(s) (N3)
             and/or having presence of distant metastasis (M1).

          -  Surgical treatment of the primary breast cancer >5 years ago.

          -  History or presence of residual or recurrent breast cancer.

          -  History or presence of endometrial cancer.

          -  History or presence of any other malignancy (besides breast cancer and endometrial
             cancer) within the past 5 years, except for adequately treated basal cell carcinoma of
             the skin.

          -  Diagnostic findings suspicious for any malignancy.

          -  Double layer endometrial thickness >8 mm as assessed by TVUS in subjects not being
             treated with tamoxifen.

          -  Final diagnosis of endometrial biopsy different from inactive/atrophic

          -  Existence of endometrial polyps as demonstrated by TVUS.

          -  Undiagnosed vaginal bleeding.

          -  Abnormal cervical smear (corresponding to PAP IIb or higher)

          -  Any previous or current unopposed estrogen administration in women with an intact
             uterus (occasional use of estrogen-containing vaginal cream was allowed after an
             appropriate washout period - see below).

          -  Use of systemic estrogens and/or progestogens (including intra-uterine progestogen
             therapy) and/or tibolone and/or phytoestrogens within 8 weeks prior to baseline; use
             of transdermal hormone therapy and/or local estrogen applications and/or non-hormonal
             medication for vasomotor symptoms within 4 weeks prior to baseline.

          -  Use of progestogen implants or injections and/or estrogen/progestogen injectable
             therapy within the past 6 months.

          -  Use of estrogen implants or injections within the past 5 years.

          -  Use of raloxifene hydrochloride and/or any non-registered investigational drug within
             the last 8 weeks.

          -  Active deep vein thrombosis, thromboembolic disorders, or a documented history of
             these conditions.

          -  Severe liver disorders.

          -  Abnormal laboratory values considered to be clinically relevant by the investigator.

          -  Any disease or condition that is clinically relevant and which, in the opinion of the
             investigator, would jeopardize the subject's well-being during the course of the
             trial.

          -  Known hypersensitivity to tibolone or any of its components

          -  Known or suspected pregnancy

          -  Age <40 years at baseline and planned breast cancer therapy <2 years after baseline