Androgen Deprivation Therapy on Bone Mineral Density Change in Prostate Cancer Patients

The Impact of Continuous Versus Intermittent Androgen Deprivation Therapy on Bone Mineral Density Change in Prostate Cancer Patients: A Multicenter, Randomized Clinical Trial

Androgen deprivation therapy (ADT) is a mainstay of prostate cancer treatment to improve overall survival for intermediate- and high-risk localized disease as well as metastatic disease. While ADT improves survival, it can cause significant morbidity and a decrement in quality of life. In particular, ADT is associated with decrease in bone mineral density (BMD) and increased risk of fracture.

Although current guidelines recommend continuous androgen deprivation therapy (CAD) as standard therapy for high-risk disease, there has been increasing recognition of adverse effects from CAD. Since 1986, intermittent androgen deprivation therapy (IAD) as alternative therapeutic strategy for prostate cancer has been proposed to delay development of castration resistance and to reduce the side effects of ADT.

While both CAD and IAD are commonly used in real clinical practice, no prior study examined BMD change after CAD or IAD, and assessed whether bone loss would recover during off-treatment of IAD. The investigators therefore determine the rate of change in BMD induced by ADT (CAD versus IAD) in men with prostate cancer.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Drug: Bicalutamide; Drug: Flutamide; Drug: Goserelin; Drug: Leuprorelin; Drug: Triptorelin; Drug: Degarelix; Drug: Maximum androgen blockade

Detailed Description

Objective: To determine the rate of bone mass loss induced by two therapeutic strategies of ADT (CAD versus IAD) in men with prostate cancer.

Design, setting, and participants: the investigators will perform randomized, open label clinical trial. Men aged over 50 yrs old with prostate cancer (localized, locally advanced, metastatic prostate cancer) who are treated with primary ADT for newly diagnosed prostate cancer or salvage ADT at biochemical recurrence following radical prostatectomy will be included.

Participants will be randomly assigned to one of the following treatment arms:

Arm 1 (CAD): ADT without any discontinuation during study period (12 months).

Arm 2 (IAD): ADT for the first 6 months of study period, if the prostate-specific antigen (PSA) reaches its nadir (< 4 ng/dL) and serum testosterone reaches castration level (< 50 ng/dL).

Outcomes:

Primary outcome: change of L-spine total BMD. Secondary outcomes: change of femur neck BMD, incidence rate of osteoporosis, risk of 10 year major osteoporotic fracture, quality of life based on Expanded Prostate Cancer Index (EPIC) questionnaire.

Timing of outcome measurement: at baseline and up to 12 months after randomization.

Statistical analyses: student's t test for continuous outcomes and Fisher's exact or chi-square test for dichotomous outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jinsung Park, MD. PhD.; Phone Number: +82426113533; Email: jspark.uro@gmail.com

Study Locations

• Korea, Republic of
  • Cheongju, Korea, Republic of
    • Recruiting
    • Department of Urology, Chungbuk National University, College of Medicine
    • Contact: Seok Joong Yun, MD. PhD.
  • Daegu, Korea, Republic of
    • Recruiting
    • Department of Urology, Kyungpook National University, School of Medicine
    • Contact: Tae-Hwan Kim, MD. PhD.
  • Daegu, Korea, Republic of
    • Recruiting
    • Department of Urology, Yeungnam University, College of Medicine
    • Contact: Phil Hyun Song, MD. PhD.
  • Daejeon, Korea, Republic of
    • Recruiting
    • Department of Urology, Eulji University, College of Medicine
    • Contact: Jinsung Park, MD. PhD.
    • Contact: Dae Seon Yoo, MD. PhD.
  • Daejeon, Korea, Republic of
    • Recruiting
    • Department of Urology, Konyang University, College of Medicine,
    • Contact: Hyung Joon Kim, MD.
  • Gwangju, Korea, Republic of
    • Recruiting
    • Department of Urology, Chonnam National University, School of Medicine
    • Contact: Eu Chang Hwang, MD. PhD.
  • Iksan, Korea, Republic of
    • Recruiting
    • Department of Urology, Wonkwang University, School of Medicine
    • Contact: Seung Chol Park, MD. PhD.
  • Jeonju, Korea, Republic of
    • Recruiting
    • Department of Urology,Jeonbuk National University Medical School
    • Contact: Young Beom Jeong, MD. PhD.
  • Pusan, Korea, Republic of
    • Recruiting
    • Department of Urology, Pusan National University, School of Medicine
    • Contact: Sung Woo Park, MD. PhD.
  • Wonju, Korea, Republic of
    • Recruiting
    • Department of Urology, Yonsei University Wonju College of Medicine
    • Contact: Jae Hung Jung, MD. PhD.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Men aged over 50 yrs old with histologically diagnosed prostate cancer (localized, locally advanced, metastatic prostate cancer) who are treated with primary ADT for newly diagnosed prostate cancer or salvage ADT at biochemical recurrence following radical prostatectomy. .

Exclusion Criteria:

1. men with double primary malignancies,
2. men who have been treated with ADT or other drug therapy such as denosumab, bisphosphonate or steroid,
3. men with osteoporosis at baseline (T-score ≤ -2.5),
4. men with a known bone disease,
5. men with poor performance status (i.e. Eastern Cooperative Oncology Group performance status 4),
6. men with life expectancy < 12 months,
7. men with increased serum PSA levels (≥ 4 ng/dL) or testosterone levels (≥ 50 ng/dL) even after 6 month ADT,
8. men who are not able to understand trial information or informed consent,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intermittent Androgen Deprivation; ADT including luteinizing hormone-releasing hormone (LHRH) agonist and antagonist, antiandrogen, or maximum androgen blockade (MAB) should be withdrawn after 6 months of ADT, if the prostate-specific antigen (PSA) reaches its nadir (< 4 ng/dL) and serum testosterone reaches castration level (< 50 ng/dL).	Drug: Bicalutamide; Antiandrogen; Other Names: Casodex; Drug: Flutamide; Antiandrogen; Other Names: Niftolide; Drug: Goserelin; LHRH agonist; Other Names: Goserelin acetate; Drug: Leuprorelin; LHRH agonist; Other Names: Leuprorelin acetate; Drug: Triptorelin; LHRH agonist; Other Names: Triptorelin acetate; Drug: Degarelix; LHRH antagonist; Other Names: Degarelix acetate; Drug: Maximum androgen blockade; Combination therapy with LHRH agonist and antiandrogen; Other Names: LHRN agonist and antiandrogen
ACTIVE_COMPARATOR: Continuous Androgen Deprivation; ADT including LHRH agonist and antagonist, antiandrogen, or MAB without any discontinuation during study period.	Drug: Bicalutamide; Antiandrogen; Other Names: Casodex; Drug: Flutamide; Antiandrogen; Other Names: Niftolide; Drug: Goserelin; LHRH agonist; Other Names: Goserelin acetate; Drug: Leuprorelin; LHRH agonist; Other Names: Leuprorelin acetate; Drug: Triptorelin; LHRH agonist; Other Names: Triptorelin acetate; Drug: Degarelix; LHRH antagonist; Other Names: Degarelix acetate; Drug: Maximum androgen blockade; Combination therapy with LHRH agonist and antiandrogen; Other Names: LHRN agonist and antiandrogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of L-spine total BMD	Measured by bone densitometry	At baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of femur neck BMD	Measured by bone densitometry	At baseline and 12 months
Osteoporosis	Defined as newly diagnosed osteoporosis based on T-score (≤ -2.5)	At 12 months
Risk of 10 year major osteoporotic fracture	Estimated by Fracture Risk Assessment Tool (FRAX®, available at www.sheffield.ac.uk/FRAX)	At 12 months
Quality of life after treatment	Measured by EPIC questionnaire	At baseline and 12 months

Collaborators and Investigators

• Sponsor: Wonju Severance Christian Hospital
• Collaborators: Eulji University Hospital
• Investigators: Principal Investigator: Jinsung Park, MD. PhD., Department of Urology, Eulji University, College of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 23, 2020
• Primary Completion (ANTICIPATED): April 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: January 15, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (ACTUAL): January 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 29, 2021
• Last Update Submitted That Met QC Criteria: July 28, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Prostatic Neoplasms; Bone Density; Androgen Antagonists
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Fertility Agents, Female; Fertility Agents; Luteolytic Agents; Leuprolide; Goserelin; Bicalutamide; Triptorelin Pamoate; Androgens; Flutamide; Androgen Antagonists
• Other Study ID Numbers: EMC 2019-12-003-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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