Clinical trial NCT04248621: Androgen Deprivation Therapy on Bone Mineral Density Change in Prostate Cancer Patients
Official title: The Impact of Continuous Versus Intermittent Androgen Deprivation Therapy on Bone Mineral Density Change in Prostate Cancer Patients: A Multicenter, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Prostatic Neoplasms
Keywords: Androgen Antagonists
Bone Density
Prostatic Neoplasms
Lead sponsor: Wonju Severance Christian Hospital
Sponsor class: OTHER
Collaborators: name: Eulji University Hospital
First posted: 2020-01-30
Enrollment: 164
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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,

Primary outcomes:
measure: Change of L-spine total BMD
timeFrame: At baseline and 12 months
Secondary outcomes:
measure: Change of femur neck BMD
timeFrame: At baseline and 12 months
measure: Osteoporosis
timeFrame: At 12 months
measure: Risk of 10 year major osteoporotic fracture
timeFrame: At 12 months
measure: Quality of life after treatment
timeFrame: At baseline and 12 months
Other outcomes:
Locations:
city: Cheongju
country: Korea, Republic of
facility: Department of Urology, Chungbuk National University, College of Medicine
city: Daegu
country: Korea, Republic of
facility: Department of Urology, Kyungpook National University, School of Medicine
city: Daegu
country: Korea, Republic of
facility: Department of Urology, Yeungnam University, College of Medicine
city: Daejeon
country: Korea, Republic of
facility: Department of Urology, Eulji University, College of Medicine
city: Daejeon
country: Korea, Republic of
facility: Department of Urology, Konyang University, College of Medicine,
city: Gwangju
country: Korea, Republic of
facility: Department of Urology, Chonnam National University, School of Medicine
city: Iksan
country: Korea, Republic of
facility: Department of Urology, Wonkwang University, School of Medicine
city: Jeonju
country: Korea, Republic of
facility: Department of Urology,Jeonbuk National University Medical School
city: Pusan
country: Korea, Republic of
facility: Department of Urology, Pusan National University, School of Medicine
city: Wonju
country: Korea, Republic of
facility: Department of Urology, Yonsei University Wonju College of Medicine
Study officials:
affiliation: Department of Urology, Eulji University, College of Medicine
name: Jinsung Park, MD. PhD.
role: PRINCIPAL_INVESTIGATOR
References: