Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)

NCT00408863 | Completed Phase 3 DMC

• 2 other identifiers: P0588532974
• Study Type: interventional
• Target: 3,148
• Locations: 0 countries
• Sites: N/A

Brief Summary

Postmenopausal women with a history of breast cancer often suffer from climacteric symptoms such as hot flushes and sweating episodes. Conventional hormone therapy is not allowed in such patients because there are indications that hormones may cause breast cancer to recur. Tibolone is a steroid with estrogenic, progestogenic and androgenic activity and is registered for treatment of climacteric complaints. Tibolone has a pharmacologic and clinical profile that is different from conventional hormones. In contrast to conventional hormones, tibolone does not increase breast density and causes less breast pain. The LIBERATE study is a study in which the safety and efficacy of tibolone has been investigated in postmenopausal women that have been treated for breast cancer.

Conditions

Breast Cancer; Climacteric Symptoms

Keywords

Breast cancer; Tibolone; Climacteric symptoms

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Secondary outcome variables include overall survival, menopausal symptoms, bone mineral density and health-related quality of life.

  At clinical completion

Study Arms (2)

Tibolone

ACTIVE COMPARATOR

Tibolone 2.5 mg/day

Drug: tibolone

Placebo

PLACEBO COMPARATOR

Placebo

Drug: placebo

Interventions

tibolone DRUG

tibolone 2.5 mg/day

Also known as: OD-14

Tibolone

placebo DRUG

Placebo

Eligibility Criteria

• Age: Up to 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• in tamoxifen users: absence of endometrial polyps
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (4)

• Kenemans P, Kubista E, Foidart JM, Yip CH, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Beckmann MW, Bundred NJ, Egberts J, van Os S, Planellas J. Safety of tibolone in the treatment of vasomotor symptoms in breast cancer patients--design and baseline data 'LIBERATE' trial. Breast. 2007 Dec;16 Suppl 2:S182-9. doi: 10.1016/j.breast.2007.07.028.

  PMID: 17983942 BACKGROUND

• Lara LA, Cartagena-Ramos D, Figueiredo JB, Rosa-E-Silva ACJ, Ferriani RA, Martins WP, Fuentealba-Torres M. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2023 Aug 24;8(8):CD009672. doi: 10.1002/14651858.CD009672.pub3.

  PMID: 37619252 DERIVED

• Sismondi P, Kimmig R, Kubista E, Biglia N, Egberts J, Mulder R, Planellas J, Moggio G, Mol-Arts M, Kenemans P. Effects of tibolone on climacteric symptoms and quality of life in breast cancer patients--data from LIBERATE trial. Maturitas. 2011 Dec;70(4):365-72. doi: 10.1016/j.maturitas.2011.09.003. Epub 2011 Oct 26.

  PMID: 22030384 DERIVED

• Kenemans P, Bundred NJ, Foidart JM, Kubista E, von Schoultz B, Sismondi P, Vassilopoulou-Sellin R, Yip CH, Egberts J, Mol-Arts M, Mulder R, van Os S, Beckmann MW; LIBERATE Study Group. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol. 2009 Feb;10(2):135-46. doi: 10.1016/S1470-2045(08)70341-3. Epub 2009 Jan 23.

  PMID: 19167925 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tibolone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2006
• First Posted: December 7, 2006
• Study Start: May 1, 2002
• Primary Completion: October 1, 2007
• Study Completion: October 1, 2007
• Last Updated: February 4, 2022

Record last verified: 2022-02