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

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.

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.

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.