Evaluation of Effects of Estetrol on Testosterone Suppression and Quality of Life in Prostate Cancer Patients Treated With an LHRH Agonist.

Study Overview
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Brief Summary
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This is a phase IIa, double-blind, randomised, placebo-controlled, multi-center study to evaluate the effects of estetrol on testosterone suppression and quality of life in prostate cancer patients treated with an LHRH agonist. Patients will be treated with estetrol or placebo for 6 months.

Official Title
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A Double-blind, Randomised, Placebo-controlled, Multi-center Study to Evaluate Effects of Estetrol on Testosterone Suppression and Quality of Life in Prostate Cancer Patients Treated With an LHRH Agonist.

Conditions
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Prostatic Neoplasm

Intervention / Treatment
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* Drug: Estetrol
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients with prostate cancer, qualifying for treatment with a LHRH agonist; Age ≥ 18 years; Body mass index (BMI) between ≥ 18.0 and ≤ 35.0 kg/m2 (inclusive); Reasonable physical and mental health as judged by the Investigator determined by physical examination, clinical laboratory assessments and vital signs; Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1; Life expectancy of at least 2 years. Exclusion Criteria: Current or prior (during the last 12 months) hormonal therapy, immunotherapy or chemotherapy for prostate cancer. Allowed are 14 days concomitant treatment with an anti-androgen to prevent the flare-up, radiotherapy and low dose radiation to prevent gynecomastia; History of deep vein thrombosis, pulmonary embolism, or cerebrovascular accident. However, patients with such history using anticoagulants for ≥ 6 months are eligible for the study provided anticoagulant treatment is continued throughout the whole study; History of myocardial infarction or a coronary vascular procedure (e.g. percutaneous coronary intervention, coronary artery bypass graft). However, patients with such history using anticoagulants for ≥ 6 months are eligible for the study provided anticoagulant treatment is continued throughout the whole study; Patients who have unstable angina or clinical congestive heart failure; A defect in the blood coagulation system, assessed at screening: deficiencies in AT-III, protein C and protein S and elevated factor VIII; Mutation in coagulation factor II and/or positive for factor V Leiden, assessed at screening; Diabetes mellitus with poor glycaemic control in the past 6 months (haemoglobin A1c (HbA1c) above 7.5%); Known primary hyperlipidaemias (Fredrickson); Disturbance of liver function: cholestatic jaundice, a history of jaundice due to previous estrogen use, Rotor syndrome and Dubin-Johnson syndrome; Known porphyria; Uncontrolled hypertension, i.e. systolic blood pressure 160 mmHg and/or diastolic blood pressure 100 mmHg in the last 6 months with or without medication.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: estetrol<br> | Drug: Estetrol<br>* estetrol formulated in tablets<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo Oral Tablet<br>* placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in total testosterone levels between treatment groups | Serum concentrations of total testosterone will be listed and summarized descriptively by treatment group. Nadir and time to nadir will be described using summary statistics. | 168 days | 
| Difference in free testosterone levels between treatment groups | Serum concentrations of free testosterone will be listed and summarized descriptively by treatment group. Nadir and time to nadir will be described using summary statistics. | 168 days | 
| Difference in mean daily hot flushes score between treatment groups | The number and severity in hot flushes will be assessed by means of a diary in which the patients records his hot flushes for 7 days. | 168 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in endocrine parameters, adrenal androgen, dihydrotestosterone (DHT) and Sex Hormone Binding Globulin (SHBG) | Effects on endocrine parameters (Luteinising Hormone (LH), Follicle Stimulating Hormone (FSH) and Estradiol (E2), adrenal androgens (Dehydroepiandrosterone sulfate (DHEAS)), dihydrotestosterone (DHT) and SHBG will be evaluated. Actual values at baseline and at the scheduled visits, as well as change from baseline values at the post-baseline visits will be described using summary statistics and graphs. Difference between the treatment groups will be evaluated. | 168 days | 
| Change from baseline in prostate-specific antigen (PSA) response | Effects on PSA response will be evaluated. Actual values at baseline and at the scheduled visits, as well as change from baseline and percentage change from baseline values at the post-baseline visits will be described using summary statistics and graphs. Nadir and time to nadir will be described using summary statistics. Difference between the treatment groups will be evaluated. | 168 days | 
| Questionnaire on Quality of Life | Effects on FACT-P questionnaire will be evaluated. FACT-P includes a 27-item core quality of life measure (FACT-G) grouped into 4 sub-scales: physical, social/family, emotional, and functional well-being. The prostate cancer-specific subscale contains an additional 12 items; 10 of which are prostate cancer specific physical problems. Items are rated on a 5-item Likert scale, from 0, not at all, to 4, very much. Total range of scores is from 0 - 156. Higher scores indicate higher degree of functioning and better quality of life. Total FACT-P scores, FACT-P general health subscale score (FACT-G) total score and all FACT-P subscale scores will be described at the scheduled visits using summary statistics and graphs. Differences between the treatment groups will be evaluated. | 168 days | 
| Change from baseline in lipids | Effects on total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol and Low Density Lipoprotein (LDL) cholesterol will be evaluated. Actual values at baseline and at the schedule visits as well as change from baseline values at the post-baseline visits will be described using summary statistics and graphs. Differences between the treatment groups will be evaluated. | 168 days | 
| Change from baseline in bone turnover markers | Effects on bone turnover markers osteocalcin and type I collagen telopeptide (CTX-1) will be evaluated. Actual values at baseline and at the schedule visits as well as change from baseline values at the post-baseline visits will be described using summary statistics and graphs. Differences between the treatment groups will be evaluated. | 168 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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quality of life, hot flushes, prostate cancer, testosterone