Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

Breast Neoplasms

Osteoporosis, Postmenopausal

Osteoporosis

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Menopause

Antineoplastic Agents

Antihypertensive Agents

All Drugs and Chemicals

Tibolone

Androgens

Androgen Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogens

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Anabolic Androgenic Steroids

Anabolic Agents

Judy Garber, MD, MPH

Women undergoing surgical menopause often experience marked menopausal side effects but are reluctant to use estrogen or other female hormones to ease the transition to menopause because of worries that the hormones may increase breast cancer risks. This study will evaluate tibolone in women experiencing surgical menopause to assess its effects on bone health, menopause symptoms and breast density.

Women interested in participating in this study will be allowed to use hormones to manage symptoms for up to 3 months before beginning the study. Those choosing not to take hormones may enroll in the study immediately.

All women will have a baseline mammogram, breast examination, and bone study density performed, along with blood and urine analysis for measurement of bone markers. They will also be asked to take a questionnaire.

Patients will take either tibolone or placebo once daily for 1 year. Neither the patient or the physician will be aware of which treatment a woman is taking during the study.

Patients will return at 6 and 12 months to have a physical examination, blood work, urine collection and bone studies. At one year, a repeat mammogram will be performed. There are also some questionnaires asking about menopause symptoms that will be performed at intervals during the study.

It is also recommended that patients take calcium and vitamin D throughout the study.

Effects of Tibilone on Bone Density, Menopause Symptoms and Breast Density in Women After Prophylactic Oophorectomy

A Randomized Study of the Effects of Tibolone on Bone Density, Menopause Symptoms and Breast Density in High Risk Women After Prophylactic Oophorectomy

Brigham and Women's Hospital

Beth Israel Deaconess Medical Center

Massachusetts General Hospital

United States Department of Defense

Dana-Farber Cancer Institute

Symptoms and General Pathology

Recurrence

Breast Diseases

Skin Diseases

tibolone

placebo

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.

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.

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

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

Organon and Co

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Leiomyoma

Myofibroma

Endometriosis

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

Reproductive Control Agents

Leuprolide

GnRH-a depot (11.25mg IM x 1) and daily Tibolone 2.5mg orally once a day for 2-3 months.

Tibolone oral therapy for 2-3 months: All participants will take a Tibolone 2.5 mg tablet orally daily, at the same time each day, following a scheduled, luteal-phase injection of leuprolide acetate 11.25mg intramuscular (IM).

Tibolone 2.5 Mg Oral Tablet

Andrew Zakhari, M.D.

While there are many medical options for managing endometriosis and fibroids, GnRH-agonist (GnRH-a) therapy remains a very common method of treating these complex conditions. Although this therapy is effective, it does come with significant menopausal side effects, such as hot flashes, sweating, mood changes, sleep disturbance, altered sex drive, decreased bone density, and vaginal and urinary symptoms.

In short, chemically-induced menopause (menopause triggered by GnRH-a injection) causes the same symptoms of natural menopause, but with a sudden onset in a generally young and active population. Low dose hormone add-back therapy is commonly used to lessen these side effects of GnRH-a use.

There are many menopausal hormone therapies (MHTs) used in menopausal women that can help, but few studies have directly evaluated the different options of treatment for women undergoing chemically-induced menopause. Tibolone is a menopausal hormone therapy (MHT) that stands out as a good option in the management of medical menopause in endometriosis patients because it may give fewer side effects than other alternatives and have a positive effect on mood and libido.

This study aims to see how effective Tibolone is as an add-back therapy in women who are hormonally suppressed with a GnRH-a. For this study, we will recruit pre-menopausal women over the age of 18 years old undergoing therapy with the GnRH-a Lupron.

Endometriosis is a common condition affecting approximately one in ten women, with significant adverse effects on women's quality of life and reproductive health. While there are numerous medical options for managing pain symptoms and reducing lesion size, GnRH-a therapy remains a mainstay of treating this complex condition. Similarly, uterine fibroids can cause heavy bleeding with associated anemia, and bulk symptoms, which may require surgical management. These hormone-sensitive fibroids regress and bleeding subsides when treatment with GnRH-a is used. This generally young and otherwise healthy population undergoes suppression of the hypothalamic-pituitary-ovarian axis in order to manage symptoms of either endometriosis or fibroids, or both if present concomitantly.

The efficacy of GnRH-a therapy has been extensively demonstrated in the literature albeit at the cost of significant menopausal side effects such as vasomotor symptoms, mood changes, sleep disturbance, altered libido, decreased bone mineral density, and genitourinary symptoms. In short, chemically-induced menopause confers the validated symptoms of natural menopause, but with an abrupt onset in a generally young and active population.

Add-back therapy with low-dose hormonal preparations is commonly used to mitigate the unwanted but largely inevitable adverse effects of GnRH-a use. Theoretically, any menopausal hormone therapy (MHT) used in menopausal women could serve the purpose, however few studies have evaluated directly the differing options in this unique population. One MHT preparation that stands out as a valuable option in the management of medical menopause in endometriosis patients is Tibolone. Tibolone is a synthetic steroid prodrug with active metabolites that exhibit estrogenic, progestogenic, and androgenic activity.

Prior studies have demonstrated that add-back treatment with Tibolone significantly reduces bone mineral density loss and vasomotor symptoms that normally occur with GnRH-a treatment. In addition, Tibolone has been shown to cause significantly fewer bleeding and spotting episodes and less breast tenderness than combined hormone replacement therapy (HRT) preparations, and has also been shown to improve mood and libido in menopausal women, making it a unique and attractive option in younger women undergoing temporary, chemical menopause.

This is a prospective open-label observational cohort study. Pre-menopausal women over 18 years of age with known or suspected endometriosis or uterine fibroids who will be undergoing treatment with an injectable GnRH-agonist (leuprolide acetate) at the Royal Victoria Hospital (Glen site) will be recruited and screened for exclusion criteria. Consenting participants of the study will receive a phone call before their GnRH-a treatment to report menopausal symptoms and endometriosis symptoms in a baseline evaluation. After their GnRH-a treatment, participants will be contacted, by phone call, one, two and three months post treatment to be asked a standardized set of questions to evaluate relief of menopausal symptoms, control of endometriosis symptoms, as well as adherence to treatment, and side-effects. Add-back will commence one month after the initial injection of GnRH-a, such that the incidence of vasomotor symptoms and other side-effects of GnRH-a may be observed. In this way, this is a crossover study by design in which patients will serve as their own controls, before and after initiating add-back therapy with Tibolone. Participants will always reserve the right to commence Tibolone sooner than 1 month if they experience bothersome side-effects.

Evaluating Tibolone Add-back in Patients With Endometriosis and Fibroids

Patient reported relief of menopausal symptoms will be evaluated using the Menopause rating scale (MRS).

The MRS is a validated 11-item health-related quality of life scale (HRQoL), that measures the presence and severity of menopausal symptoms.

Patient reported relief of sexual dysfunction (a menopausal symptom) will be evaluated using the Abbreviated female sexual function index (AFSFI).

The abbreviated FSFI is a validated 6-item self-report questionnaire designed to assess female sexual function, comprised of six domains: desire, arousal, lubrication, orgasm, satisfaction, and pain.

Control of endometriosis symptoms will be evaluated using a modified Biberoglu \& Behrman (B\&B) scale. This is a validated scale that evaluates endometriosis pain by patient's self-assessment of three pain symptoms (dysmenorrhea, dyspareunia, and chronic pelvic pain).

This will be discussed during the monthly phone call with the participant.

McGill University Health Centre/Research Institute of the McGill University Health Centre

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effects of Tibilone on Bone Density, Menopause Symptoms and Breast Density in Women After Prophylactic Oophorectomy	NCT00165204	Menopause Postmenopausal ... Breast Cancer	Tibolone	18 Years -	Dana-Farber Cancer Institute
Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)	NCT00408863	Breast Cancer Climacteric Sym...	tibolone placebo	- 75 Years	Organon and Co
Effects of Tibilone on Bone Density, Menopause Symptoms and Breast Density in Women After Prophylactic Oophorectomy	NCT00165204	Menopause Postmenopausal ... Breast Cancer	Tibolone	18 Years -	Dana-Farber Cancer Institute
Evaluating Tibolone Add-back in Patients With Endometriosis and Fibroids	NCT05568940	Endometriosis Fibroids	Tibolone 2.5 Mg...	18 Years -	McGill University Health Centre/Research Institute of the McGill University Health Centre
Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885)	NCT00408863	Breast Cancer Climacteric Sym...	tibolone placebo	- 75 Years	Organon and Co
Evaluating Tibolone Add-back in Patients With Endometriosis and Fibroids	NCT05568940	Endometriosis Fibroids	Tibolone 2.5 Mg...	18 Years -	McGill University Health Centre/Research Institute of the McGill University Health Centre
Evaluating Tibolone Add-back in Patients With Endometriosis and Fibroids	NCT05568940	Endometriosis Fibroids	Tibolone 2.5 Mg...	18 Years -	McGill University Health Centre/Research Institute of the McGill University Health Centre

Spots Global Cancer Trial Database for tibolone

Every month we try and update this database with for tibolone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tibolone

Every month we try and update this database with for tibolone cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tibolone cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.