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CompletedNCT03361969Updated Jun 18, 2021

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

A Phase 2 interventional study of Estetrol and Placebo Oral Tablet in Prostatic Neoplasm, sponsored by Pantarhei Oncology B.V.. Completed at 6 sites in Netherlands. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-18.

Sponsored by Pantarhei Oncology B.V. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
63
Allocation
Randomized
Ages
18 Years and older
Sex
Male
01

Study 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.

02

Conditions studied

  • Prostatic Neoplasm

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Keywords

  • quality of life
  • hot flushes
  • prostate cancer
  • testosterone
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
63 participants (actual)

Study arms

  • Active comparator
    estetrol

    Drug: Estetrol

  • Placebo comparator
    placebo

    Drug: Placebo Oral Tablet

Interventions

  • DrugEstetrol

    estetrol formulated in tablets

  • DrugPlacebo Oral Tablet

    placebo tablets

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 168 days

  2. 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.

    Time frame: 168 days

  3. 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.

    Time frame: 168 days

Secondary outcomes

  1. 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.

    Time frame: 168 days

  2. 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.

    Time frame: 168 days

  3. 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.

    Time frame: 168 days

  4. 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.

    Time frame: 168 days

  5. 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.

    Time frame: 168 days

06

Study locations

6 sites
  • Andros Men's Health Institutes
    Arnhem, Gelderland 6803 AA, Netherlands
  • Noord West Ziekenhuis
    Alkmaar, Netherlands
  • St Antonius Ziekenhuis
    Nieuwegein, Netherlands
  • CWZ
    Nijmegen, Netherlands
  • Antonius Ziekenhuis
    Sneek, Netherlands
  • Isala Zwolle
    Zwolle, Netherlands
07

Registry details

Key details

Study ID
NCT03361969
Lead sponsor
Pantarhei Oncology B.V.
Responsible party
Sponsor
First posted
Dec 5, 2017
Start date
Apr 16, 2018
Primary completion
May 15, 2020
Completion
May 15, 2020
Last update
Jun 18, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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