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.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasm
• Intervention / Treatment: Drug: Estetrol; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands
    • Noord West Ziekenhuis
  • Nieuwegein, Netherlands
    • St Antonius Ziekenhuis
  • Nijmegen, Netherlands
    • CWZ
  • Sneek, Netherlands
    • Antonius Ziekenhuis
  • Zwolle, Netherlands
    • Isala Zwolle
  • Gelderland
    • Arnhem, Gelderland, Netherlands, 6803 AA
      • Andros Men's Health Institutes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo	Drug: Placebo Oral Tablet; placebo tablets
ACTIVE_COMPARATOR: estetrol	Drug: Estetrol; estetrol formulated in tablets

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pantarhei Oncology B.V.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 16, 2018
• Primary Completion (ACTUAL): May 15, 2020
• Study Completion (ACTUAL): May 15, 2020

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 28, 2017
• First Posted (ACTUAL): December 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: quality of life; prostate cancer; hot flushes; testosterone
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PR3109

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No