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

• ClinicalTrials.gov Identifier: NCT03361969
• Recruitment Status: Completed
• First Posted: December 5, 2017
• Last Update Posted: June 18, 2021
• Sponsor: Pantarhei Oncology B.V.
• Information provided by (Responsible Party): Pantarhei Oncology B.V.

Tracking Information

• First Submitted Date: November 21, 2017
• First Posted Date: December 5, 2017
• Last Update Posted Date: June 18, 2021
• Actual Study Start Date: April 16, 2018
• Actual Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2017)

• Difference in total testosterone levels between treatment groups [ Time Frame: 168 days ]
  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.
• Difference in free testosterone levels between treatment groups [ Time Frame: 168 days ]
  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.
• Difference in mean daily hot flushes score between treatment groups [ Time Frame: 168 days ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 28, 2017)

• Change from baseline in endocrine parameters, adrenal androgen, dihydrotestosterone (DHT) and Sex Hormone Binding Globulin (SHBG) [ Time Frame: 168 days ]
  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.
• Change from baseline in prostate-specific antigen (PSA) response [ Time Frame: 168 days ]
  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.
• Questionnaire on Quality of Life [ Time Frame: 168 days ]
  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.
• Change from baseline in lipids [ Time Frame: 168 days ]
  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.
• Change from baseline in bone turnover markers [ Time Frame: 168 days ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Effects of Estetrol on Testosterone Suppression and Quality of Life in Prostate Cancer Patients Treated With an LHRH Agonist.
• Official Title: 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.
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Prostatic Neoplasm

Intervention

• Drug: Estetrol
  estetrol formulated in tablets
• Drug: Placebo Oral Tablet
  placebo tablets

Study Arms

• Active Comparator: estetrol
  Intervention: Drug: Estetrol
• Placebo Comparator: placebo
  Intervention: Drug: Placebo Oral Tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 16, 2021): 63
• Original Estimated Enrollment (submitted: November 28, 2017): 60
• Actual Study Completion Date: May 15, 2020
• Actual Primary Completion Date: May 15, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03361969
• Other Study ID Numbers: PR3109
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pantarhei Oncology B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Pantarhei Oncology B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Pantarhei Oncology B.V.
• Verification Date: June 2021