AzTrials
AzTrials

Breast CancerPhase 3NCT00408863

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

A Phase 3 study testing tibolone in people with Breast Cancer and Climacteric Symptoms, run by Organon and Co.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages Up to 75 years, women only
Conditions the study is for
Breast Cancer, Climacteric Symptoms
What is being tested?
tibolone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,148 participants
Where
No sites listed yet
Study dates
May 2002to Oct 2007
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 75 years
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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

About this study

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

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.

Read the 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.

Being tested
tibolone, placebo
Keywords
Breast cancer, Tibolone, Climacteric symptoms
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tiboloneDrug

    Also called OD-14

    tibolone 2.5 mg/day

  • placeboDrug

Study groups in NCT00408863
Study groupRoleWhat they receive
TiboloneActive comparatorTibolone 2.5 mg/day
Receives: Drug: tibolone
PlaceboPlacebo comparatorPlacebo
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: At clinical completion

Secondary outcomes (1)

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

    Measured: At clinical completion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2006 (estimated)
  2. Study startMay 2002
  3. Primary completionOct 2007
  4. Study completionOct 2007

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
3,148 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00408863
Sponsor's protocol ID
P05885
Other IDs
32974
Status last verified
Feb 2022
First submitted
6 Dec 2006
Last updated
4 Feb 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 17983942

  • 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.

    PubMed 37619252

  • 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.

    PubMed 22030384

  • 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.

    PubMed 19167925

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing tibolone in people with Breast Cancer and Climacteric Symptoms, run by Organon and Co.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00408863, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in