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

Primary Purpose

Prostatic Neoplasm

Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Estetrol
Placebo Oral Tablet
Sponsored by
Pantarhei Oncology B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostatic Neoplasm focused on measuring quality of life, hot flushes, prostate cancer, testosterone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Andros Men's Health Institutes
  • Noord West Ziekenhuis
  • St Antonius Ziekenhuis
  • CWZ
  • Antonius Ziekenhuis
  • Isala Zwolle

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

estetrol

placebo

Arm Description

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.

Full Information

First Posted
November 21, 2017
Last Updated
June 16, 2021
Sponsor
Pantarhei Oncology B.V.
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1. Study Identification

Unique Protocol Identification Number
NCT03361969
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
April 16, 2018 (Actual)
Primary Completion Date
May 15, 2020 (Actual)
Study Completion Date
May 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pantarhei Oncology B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasm
Keywords
quality of life, hot flushes, prostate cancer, testosterone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
estetrol
Arm Type
Active Comparator
Arm Title
placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Estetrol
Intervention Description
estetrol formulated in tablets
Intervention Type
Drug
Intervention Name(s)
Placebo Oral Tablet
Intervention Description
placebo tablets
Primary Outcome Measure Information:
Title
Difference in total testosterone levels between treatment groups
Description
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.
Time Frame
168 days
Title
Difference in free testosterone levels between treatment groups
Description
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.
Time Frame
168 days
Title
Difference in mean daily hot flushes score between treatment groups
Description
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.
Time Frame
168 days
Secondary Outcome Measure Information:
Title
Change from baseline in endocrine parameters, adrenal androgen, dihydrotestosterone (DHT) and Sex Hormone Binding Globulin (SHBG)
Description
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.
Time Frame
168 days
Title
Change from baseline in prostate-specific antigen (PSA) response
Description
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.
Time Frame
168 days
Title
Questionnaire on Quality of Life
Description
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.
Time Frame
168 days
Title
Change from baseline in lipids
Description
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.
Time Frame
168 days
Title
Change from baseline in bone turnover markers
Description
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.
Time Frame
168 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Andros Men's Health Institutes
City
Arnhem
State/Province
Gelderland
ZIP/Postal Code
6803 AA
Country
Netherlands
Facility Name
Noord West Ziekenhuis
City
Alkmaar
Country
Netherlands
Facility Name
St Antonius Ziekenhuis
City
Nieuwegein
Country
Netherlands
Facility Name
CWZ
City
Nijmegen
Country
Netherlands
Facility Name
Antonius Ziekenhuis
City
Sneek
Country
Netherlands
Facility Name
Isala Zwolle
City
Zwolle
Country
Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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