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

February 2, 2022 updated by: Organon and Co

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

3148

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: placebo
Active Comparator: Tibolone
Tibolone 2.5 mg/day
Drug: tibolone
tibolone 2.5 mg/day
Other Names:
  • OD-14

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
At clinical completion

Secondary Outcome Measures

Outcome Measure
Time Frame
Secondary outcome variables include overall survival, menopausal symptoms, bone mineral density and health-related quality of life.
Time Frame: At clinical completion
At clinical completion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Organon and Co

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2002

Primary Completion (Actual)

October 1, 2007

Study Completion (Actual)

October 1, 2007

Study Registration Dates

First Submitted

December 6, 2006

First Submitted That Met QC Criteria

December 6, 2006

First Posted (Estimate)

December 7, 2006

Study Record Updates

Last Update Posted (Actual)

February 4, 2022

Last Update Submitted That Met QC Criteria

February 2, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P05885
  • 32974

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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