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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00408863
First received: December 6, 2006
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Climacteric Symptoms
Drug: tibolone
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: At clinical completion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary outcome variables include overall survival, menopausal symptoms, bone mineral density and health-related quality of life. [ Time Frame: At clinical completion ] [ Designated as safety issue: Yes ]

Enrollment: 3148
Study Start Date: May 2002
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tibolone
Tibolone 2.5 mg/day
Drug: tibolone
tibolone 2.5 mg/day
Other Name: OD-14
Placebo Comparator: Placebo
Placebo
Drug: placebo

Detailed Description:

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 oophorectomy).

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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00408863     History of Changes
Other Study ID Numbers: P05885, 32974
Study First Received: December 6, 2006
Last Updated: May 7, 2014
Health Authority: Australia: National Health and Medical Research Council
Austria: Agency for Health and Food Safety
Belarus: Ministry of Health
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: Ministry of Health
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Czech Republic: State Institute for Drug Control
Estonia: The State Agency of Medicine
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Latvia: State Agency of Medicines
Mexico: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Ministry of Health
Romania: National Medicines Agency
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Taiwan: Department of Health
Thailand: Ministry of Public Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Merck Sharp & Dohme Corp.:
Breast cancer
Tibolone
Climacteric symptoms

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tibolone
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Modulators
Anabolic Agents
Hormones

ClinicalTrials.gov processed this record on September 18, 2014