Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Androgens

Leuprolide

Goserelin

Triptorelin Pamoate

Androgen Antagonists

Antineoplastic Agents, Hormonal

Contraceptive Agents

Contraceptive Agents, Female

Contraceptive Agents, Hormonal

Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietician, and symptom management service to receive individualized counseling monthly for 12 months.

Receive individualized nutrition counseling

Behavioral Dietary Intervention

Receive individualized symptom management service counseling

Counseling

Educational Intervention

Receive individualized exercise counseling

Exercise Intervention

Goserelin Acetate

Laboratory Biomarker Analysis

Leuprolide Acetate

Quality-of-Life Assessment

Rahul Aggarwal, MD

This pilot partially-randomized phase II trial studies how well Supportive Therapy in Androgen Deprivation (STAND) clinic works in improving health outcomes and managing side effects in patients with prostate cancer. Individualized counseling regarding exercise and dietary habits may help improve patient understanding, satisfaction, and overall lessen adverse impact on quality of life caused by androgen deprivation.

PRIMARY OBJECTIVES:

I. To compare the mean percent change from baseline to 12 months in percentage body fat mass among men with prostate cancer receiving androgen deprivation therapy randomized to participate in the ?STAND? clinic versus (vs.) usual standard of care. (Randomized Cohort) II. To determine the feasibility of completing multi-disciplinary STAND clinic visits within context of concurrent chemohormonal therapy for prostate cancer. (Non-randomized Pilot Cohort)

SECONDARY OBJECTIVES:

I. To compare the mean percent change from baseline to 12 months and patterns of change over time during participation in the STAND clinic vs. usual standard of care with respect to: metabolic impact on diabetes and cardiovascular risk factors, bone health, and quality of life/psychosocial impact.

II. Among men randomized to receive usual standard of care that cross-over to participate in the STAND clinic after month 12 of the study: to measure the mean change from baseline at start of participation in the STAND clinic after 12 months of participation in: metabolic parameters including percentage body fat, fasting insulin/glucose, homeostatic model assessment insulin resistance (HOMA-IR), body weight/body mass index, waist circumference; bone health; quality of life; and patient satisfaction.

III. Among men in the non-randomized pilot cohort: to determine the mean change from baseline to 12 months during STAND clinic participation in the primary and secondary metabolic and quality of life parameters listed above.

TERTIARY OBJECTIVES:

I. To investigate for a relationship between inherited genetic polymorphisms of functional relevance near or within genes encoding proteins with roles in steroid hormone transport and androgen receptor signaling with changes in metabolic parameters among men treated with androgen deprivation therapy.

II. To investigate changes in trabecular bone micro-architecture as measured by high resolution peripheral quantitative computed tomography (QCT) Imaging of radius and tibia during androgen deprivation therapy.

III. To investigate for relationship between 2nd digit to 4th digit length ratio (2D:4D ratio) and quality of life on androgen deprivation therapy.

IV. To investigate for a relationship between 2nd digit to 4th digit length ratio and baseline empathy score as measured by validated questionnaire.

OUTLINE: Patients receiving androgen deprivation therapy are randomized to 1 of 2 arms and patients receiving concurrent chemohormonal therapy are assigned to Arm II.

ARM I (STANDARD OF CARE): Patients receive leuprolide acetate subcutaneously (SC) or intramuscularly (IM), goserelin acetate SC, or triptorelin pamoate IM and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

ARM II (STAND CLINIC): Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietician, and symptom management service to receive individualized counseling monthly for 12 months.

After completion of study treatment, patients are followed up at 2, 4, and 6 months.

Supportive Therapy in Androgen Deprivation Clinic in Improving Health Outcomes and Managing Side Effects in Patients With Prostate Cancer

A Multidisciplinary Team-Based Approach to Mitigate the Impact of Androgen Deprivation Therapy in Prostate Cancer: A Randomized Phase 2

The absolute change from baseline in percentage body fat after 12 months of study participation for participants in the randomized cohort was measured using a bioelectrical impedance analyzer and between group comparisons were performed using the Wilcoxon-rank-sum test.

The percentage of participants in the pilot, non-randomized cohort who completed clinic visits for Supportive Therapy in Androgen Deprivation (STAND) will be reported to assess feasibility.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in systolic and diastolic blood pressure from the baseline to month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in body weight from the baseline to month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in percentage of body fat from the baseline to the month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in waist circumference from the baseline to the month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in percentage hemoglobin A1c from the baseline to the month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in insulin resistance scores from the baseline to the month 12 assessment. Insulin resistance scores were calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This calculation marks for both the presence and extent of any insulin resistance that participants might currently express. The HOMA-IR is an assessment using insulin and glucose lab values to generate an insulin resistance score. A healthy score range is 1.0 (0.5-1.4). A score of less than 1.0 means you are insulin-sensitive which is optimal. A score above 1.9 indicates early insulin resistance. A score above 2.9 indicates significant insulin resistance. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic and cardiac impact for participants in the randomized cohort was measured by calculating the absolute change in fasting lipids which includes total cholesterol, low density lipoprotein, High density lipoprotein, and triglycerides levels from the baseline to the month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

Metabolic impact for participants from baseline to 12 months was measured using an exercise pattern questionnaire. The questionnaire measured self-reported average total time per week over the past year the participant participated in various physical activities such as walking, tennis, yoga, swimming, etc. Twelve response options for each activity are as follows: None, 1-4 minutes (min), 5-19 min, 20-39 min, 40-89 min, 1.5 hours, 2-3 hours, 4-6 hours, 7-10 hours, 11-20 hours, 21-30 hours, 31-40 hours, 40+ hours. The amount of time per week spent on each activity was converted to a hourly scale and the absolute change between baseline and month 12 times were calculated for each participant. The median absolute change in hours per week were compared for each of the 6 activity categories: non-vigorous, moderate, moderate-vigorous, vigorous, and total physical activity and total moderate and vigorous activity combined.

Metabolic impact for participants in each group from baseline to 12 months was measured by using an ambulatory accelerometer worn by participants around their waist for 7 consecutive days. Participants were required at least 3 days of valid wear time, defined as \>= 10 hours of wear per day. The accelerometer measured movement intensity and recorded vertical acceleration as "counts," providing an indication of the intensity of physical activity associated with locomotion. Non-wear time was identified using Troiano 2007 default settings in the ActiLife v6.13.3 software. The amount of time participants were engaged in moderate to vigorous physical activities (MVPA) was measured by accelerometer as counts per minute (moderate activity = 2020-5998 counts per minute, and vigorous activity = 5999 or more counts per minute). Counts are then transformed into minutes per day with a total range of 0-1440 minutes. The median absolute change in average MVPA was compared between the two groups.

The absolute change in bone density t-scores from the baseline to the month 12 assessment for participants in the randomized cohort was measured using bone density at the lumbar spine, bone density at the femoral neck, and bone density at the total hip. A T-score of -1.0 or above is normal bone density. A T-score between -1.0 and -2.5 indicates low bone density or osteopenia. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The absolute change in bone health parameters as measured by the serum 25-(OH) vitamin D level from the baseline to the month 12 assessment. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The absolute change in scores on the Patient Health Questionnaire-9 (PHQ-9) from baseline after 12 months of study participation for participants was used to measure depression symptoms with a higher number indicating a greater percentage of change in scores. The total Patient Health Questionnaire-9 (PHQ-9) score is calculated by combining the responses of the participant on questions addressing how bothered the participant has been by various problems over the past 2 weeks. Each of the 9 items is scored on a scale of 0 ("Not bothered at all") to 4 ("Nearly every day"). A total score of 5-9='Mild Depression Symptoms", 10-4="Minor Depression, Major Depression (mild), or Dysthymia", 15-19="Major Depression, moderately severe", and \>20="Major Depression".

Between group comparisons were performed using the Wilcoxon-rank-sum test.

The AFI measures a participants perceived effectiveness in functioning at time of assessment. Each of the 16 items consists of a 100 mm horizontal line anchored with opposite phrases from not at all (0 mm) to extremely well or a great deal (100 mm). Subjects are asked to place a mark on the line that best describes functioning in relation to specific activity. Scores for each item are determined by measuring distance from lower end of scale in millimeters. The total score on the instrument is computed by obtaining an average of 16 scales. The absolute change in score by group from baseline up to month 12 in Attention Function Index was used to measure perceived effectiveness in common activities requiring attention and working memory in daily life with a higher number indicating a greater absolute change in scores. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The SF-12 is a 12-item questionnaire used to assess generic health outcomes from the patient's perspective. The SF-12 consists of a subset of 12 items from the SF-36® Health Survey (SF-36) and measures two composite outcomes assessing mental health composite score (MCS) and physical health composite scores (PCS). The PCS \& MCS are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The absolute change in item score by group from baseline up to 12 months was used to assess the quality of life/psychosocial impact on the patients with a larger scores indicating a greater degree of change on physical and mental health. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The absolute change in score by group from baseline up to month 12 on the International Prostate Symptom Score (IPSS) was used to measure the severity of lower urinary tract symptoms and erectile function with lower numbers indicating less change in symptoms. Seven questions with scores ranging from 1-5 are summed to create a total score. Scores of 1-7 indicate mild symptoms, scores of 8-19 indicate moderate symptoms, and scores of 20-35 indicate severe symptoms. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The absolute change in score by group from baseline up to month 12 on the International Prostate Symptom Score (IPSS) was used to measure the severity of lower urinary tract symptoms and erectile function. The last question on the IPSS can be looked at separately from the total score as it asks the participants to rate the overall quality of life due to their existing urinary symptoms on a scale of 0-6, with lower scores indicating a better quality of life. Between group comparisons were performed using the Wilcoxon-rank-sum test.

The absolute change in Hot Flash Related Daily Interference Scale from baseline to month 12 was used to measure the impact of occurrence of hot flashes on daily activities with higher numbers indicating a greater change in the interference of hot flashes with participant's quality of life. The HFRDIS is a 10-item scale measuring the degree hot flashes interfere with nine daily activities; the tenth item measures the degree hot flashes interfere with overall quality of life. The HFRDIS was developed to include daily life activities specific to impact of hot flashes. Participants rate degree to which hot flashes have interfered with each item during previous week using a 0 (do not interfere) to 10 (completely interfere) point scale, with total score ranging from 0-100. Higher scores indicate higher interference and thus, greater impact on quality of life. Women without hot flashes are asked to mark 0 for each item. Group comparisons performed using the Wilcoxon-rank-sum test.

The EPIC-26 was measured at baseline and month 12 to determine the impact of quality of life issues across 5 prostate cancer specific domains: Urinary incontinence, Urinary irritation, Bowel function, Sexual function, and Hormonal function and overall total quality of life. Response options for each EPIC item form a Likert scale, and the raw score of each item is then transformed linearly to a 0-100 scale. Multiple items are combined and then averaged to form the domain scores and total score at each time point also ranging from 0-100, with higher scores representing better health related quality of life (HRQOL). Between group comparisons were performed using the Wilcoxon-rank-sum test

The absolute change in Lee Fatigue Scale from baseline to month 12 was used to measure the impact of Fatigue on a participants quality of life. The scale consists of 18 items relating to the subjective experience of fatigue. Each item asks respondents to place an "X" representing how they currently feel, along a visual analogue line that extends between two extremes (e.g., from "not at all tired" to "extremely tired"). Each line is 100 mm in length - thus, scores fall between 0 and 100. The instrument also possesses two subscales: fatigue (items 1-5 and 11-18) and energy (items 6-10). The fatigue subscale score is calculated as the mean of the 13 fatigue items, and the energy subscale score is the mean of the 5 energy items. Higher scores on the fatigue subscale represent greater fatigue severity, and higher scores on the energy subscale indicate higher levels of energy. Between group comparisons were performed using the Wilcoxon-rank-sum test.

National Cancer Institute (NCI)

University of California, San Francisco

The Behavioral-Dietary intervention under investigation was not determined to pose any significant risk to the patient however, all grade(s) 3-5 adverse events, whether or not unexpected, and whether or not considered to be associated with the use of the study treatment were collected.

Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

Goserelin Acetate: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leuprolide Acetate: Given SC or IM

Quality-of-Life Assessment: Ancillary studies

Triptorelin Pamoate: Given IM

Arm I (Standard of Care)

Patients receive leuprolide acetate SC or IM, goserelin acetate SC, or triptorelin pamoate IM every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietician, and symptom management service to receive individualized counseling monthly for 12 months.

Behavioral Dietary Intervention: Receive individualized nutrition counseling

Counseling: Receive individualized symptom management service counseling

Educational Intervention: Review educational modules

Exercise Intervention: Receive individualized exercise counseling

Goserelin Acetate: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leuprolide Acetate: Given SC or IM

Quality-of-Life Assessment: Ancillary studies

Triptorelin Pamoate: Given IM

Arm II (STAND Clinic)

A non-randomized pilot cohort receiving concurrent chemohormonal therapy will be enrolled in parallel to assess the feasibility of STAND clinic participation in this patient population.

Non-Randomized Pilot Cohort

A non-randomized pilot cohort of 20 patients receiving concurrent chemohormonal therapy will be enrolled in parallel to assess the feasibility of STAND clinic participation in this patient population.

Total

50-60 years old

61-70 years old

71-80 years old

81-90 years old

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Absolute change calculated for outcomes and and non-parametric statistical tests performed due to small sample size from early study termination. Non-randomized pilot cohort to assess feasibility was not included in group comparisons.

Li Zhang, PhD

Patients receive leuprolide acetate SC or IM, or goserelin acetate SC, and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

Goserelin Acetate: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leuprolide Acetate: Given SC or IM

Quality-of-Life Assessment: Ancillary studies

Patients receive leuprolide acetate SC or IM, or goserelin acetate SC every 3 months for 12 months. Patients also review educational modules discussing various aspects of anti-androgen therapy and management of side effects and meet one-to-one with a licensed exercise trainer, registered dietitian, and symptom management service to receive individualized counseling monthly for 12 months.

Behavioral Dietary Intervention: Receive individualized nutrition counseling

Counseling: Receive individualized symptom management service counseling

Educational Intervention: Review educational modules

Exercise Intervention: Receive individualized exercise counseling

Goserelin Acetate: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leuprolide Acetate: Given SC or IM

Quality-of-Life Assessment: Ancillary studies

Absolute Change in Percentage Body Fat Mass as Measured by Bioelectrical Impedance Analyzer (Randomized Cohort)

Percentage of Participants in the Non-randomized, Pilot, Cohort Who Completed Clinic Visits

Systolic Blood Pressure measurement comparison

Diastolic Blood Pressure measurement comparison

Systolic Blood Pressure

Diastolic Blood Pressure

Absolute Change in Blood Pressure (Randomized Cohort)

Absolute Change in Body Weight (Randomized Cohort)

Percentage body fat measurement comparison

Absolute Change in Percentage of Body Fat (Randomized Cohort)

Absolute Change in Waist Circumference (Randomized Cohort)

Absolute Change in Hemoglobin A1c (Randomized Cohort)

Absolute Change in Insulin Resistance Score (Randomized Cohort)

Total low density lipid measurement comparison

Total high density lipid measurement comparison

Total triglyceride measurement comparison

Total Cholesterol

Low density lipoprotein

High density lipoprotein

Triglycerides

Absolute Change in Fasting Lipids (Randomized Cohort)

Non-vigorous physical activity comparison

Moderate-Vigorous physical activity comparison

Non-vigorous physical activity

Moderate physical activity

Vigorous physical activity

Total physical activity

Total Moderate-Vigorous physical activity (MVPA)

Only a small subset of patients reported both baseline and 12 month data.

Absolute Change in Hours Per Week of Physical Activity Category as Measured by the Exercise Pattern Assessment (Randomized Cohort)

Absolute Change in Average Moderate to Vigorous Physical Activity (MVPA) as Measured by an Ambulatory Accelerometer Assessment (Randomized Cohort)

Bone Density at the lumbar spine comparison

Bone Density at the femoral neck comparison

Bone density at the lumbar spine

Bone density at the femoral neck

Bone density of total hip

Absolute Change in Bone Density T-score (Randomized Cohort)

Absolute Change in Serum 25-(OH) Vitamin D (Randomized Cohort)

Absolute Change in Patient Health Questionnaire-9 (PHQ-9) Scores (Randomized Cohort)

Attention Function Index (AFI) Score Comparison

Only a subset of patients reported both baseline and 12 month data.

Absolute Change in Attention Function Index (AFI) Scores (Randomized Cohort)

Mental Composite Score

Physical Composite Score

Only a subset of participants completed questionnaires at both baseline and 12 months.

Absolute Change in the 12-item Short Form Survey (SF-12) Assessment Item Scores for Patients in the Randomized Cohort

Absolute Change in International Prostate Symptom Score (IPSS) (Randomized Cohort)

Absolute Change in Last Question on International Prostate Symptom Score (IPSS) (Randomized Cohort)

Absolute Change in Hot Flash Related Daily Interference Scale Score (HFRDIS) (Randomized Cohort)

EPIC-26 Urinary Incontinence Score Comparison

EPIC-26 Urinary Irriation Score Comparison

EPIC-26 Hormonal Function Score Comparison

Urinary incontinence

Urinary irritation

Bowel function

Sexual function

Hormonal Function

Absolute Change in Expanded Prostate Cancer Index Composite Short Form (EPIC-26) Scores to Assess Erectile and Urinary Function (Randomized Cohort)

Fatigue Scale

Energy Scale

Absolute Change in Lee Fatigue Scale Scores (Randomized Cohort)

Patients receive leuprolide acetate subcutaneous (SC) or intramuscular (IM), or goserelin acetate SC, and visit their health care provider every 3 months for 12 months. Patients will be referred to a nutrition, exercise, and symptom management service upon patient request or if deemed necessary by a healthcare provider. Patients may cross-over to Arm II after 12 months.

Goserelin Acetate: Given SC

Laboratory Biomarker Analysis: Correlative studies

Leuprolide Acetate: Given SC or IM

Quality-of-Life Assessment: Ancillary studies

Overall Study

Symptoms and General Pathology

Recurrence

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

The standard hormonal treatment in combination with salvage radiotherapy is ADT by a LHRH agonist or antagonist for 24 weeks. LHRH agonists and antagonists include leuprolide, goserelin, triptorelin, and degarelix.

Patients will receive 6 cycles (each cycle is 30 days) of the study drug (4x 60mg tablets daily in a single intake).

Apalutamide 240mg daily for 6 months (i.e. 6 28-day cycles); oral use

Apalutamide

Leuprorelin acetate 45mg for 6 months; subcutaneous use

Leuprorelin Acetate 45Mg Powder for Injection Suspension Vial

Goserelin acetate 10.8mg for 6 months; subcutaneous use

Goserelin Acetate 10.8 MG Subcutaneous Implant

Triptorelin pamoate 22.5mg for 6 months; intramuscular use

Degarelix acetate 80mg for 6 months; subcutaneous use

Degarelix acetate

Ilse Van der Auwera

Nele Smet

Peter Schatteman, MD

Christophe Ghysel, MD

Thierry Roumeguère, MD

Valerie Fonteyne, MD

Nick Liefhooghe, MD

Piet Dirix, MD, PhD

Piet Dirix

This is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist (arm A) versus anti-androgen therapy (AAT) with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of androgen-deprivation therapy (ADT) with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm) or 6 28-day cycles of apalutamide 240mg daily (interventional arm). The study will include a screening phase, treatment phase, and a post-treatment phase. The primary objective of the trial is to compare sexual function between the 2 groups based on the Expanded Prostate cancer Index Composite (EPIC)-26 sexual domain scores at 9 months after start of hormonal treatment.

After radical prostatectomy, around one third of patients will have biochemical progression. Salvage radiotherapy (SRT) is still potentially curative, but about 40-50% of patients will progress further. Recently, success rates of SRT were significantly improved through the use of concomitant anti-androgen (AAT) or androgen-deprivation (ADT) therapy. In RTOG 96-01, 2 years of bicalutamide 150 mg resulted in a 5% overall survival benefit at 12-years. In GETUG-AFU 16, 5-year progression-free survival was significantly improved when SRT was combined with 6 months of an LHRH agonist. Based on GETUG-AFU 16, most radiation oncologists now combine SRT with at least 6 months of ADT. However, ADT comes with several serious side-effects, both physical (cardiovascular, metabolic, musculoskeletal) and psychological (sexual, emotional and cognitive). It appears worthwile to look for alternatives in the form of AAT. In that respect, apalutamide, a potent competitive and purely antagonistic second-generation anti-androgen, is the ideal candidate.

This trial is a phase II randomized, open-label study comparing salvage radiotherapy in combination with 6 months of ADT (arm A) versus AAT with apalutamide 240mg daily (arm B) in hormone-naïve patients with biochemical progression after radical prostatectomy. All subjects will receive salvage radiotherapy as standard of care and will be randomly assigned in a 1:1 ratio to receive either 6 months of ADT with LHRH agonist or antagonist through 6 monthly, two 3-monthly or one 6-monthly injections (control arm A) or 6 28-day cycles of apalutamide 240mg daily (interventional arm B).

The study will include a screening phase, treatment phase, and a post-treatment phase.

1. Screening phase: allows for assessment of subject eligibility up to 35 days prior to randomization.
2. Treatment phase: includes the hormonal treatment for 6 months, to be started at the most 2 weeks after randomization and standard salvage radiotherapy. During the treatment phase, patients will have 3 study visits:

   1. treatment initiation visit: first injection of LHRH (ant)agonist (arm A) or cycle 1, day 1 (C1D1) of apalutamide (arm B).
   2. Concurrent with RT visit: if necessary (depending on product prescribed) injection of LHRH (ant)agonist (arm A) or cycle 4, day 1 (C4D1) of apalutamide (arm B).
   3. End of treatment visit: at the end of the 6 months of hormonal therapy.
3. Post-treatment phase: will begin after a subject completes the treatment phase and the end of treatment visit and will continue until the primary endpoint is reached, i.e. the 9-months (3 months after end of treatment visit) EPIC-26 sexual domain score.

The primary objective of the trial is to compare sexual function between the 2 groups based on the EPIC-26 sexual domain (0 - 100 scale, with higher scores representing better sexual function) at 9 months after start of hormonal treatment (primary endpoint). The following secondary endpoints will be explored:

1. Quality of life: assessed using EPIC-26 as well as the EORTC quality of life questionnaires C30 and PR25 as well as FACT-P.
2. Toxicity: will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
3. Efficacy: prostate-specific antigen (PSA) response rates, defined as a decline from baseline in PSA level of 80% or greater, as well as PSA complete response rates, defined as a decline from baseline in PSA level of 90% or greater, will be prospectively collected at the 4 treatment visits.

At this point in time, no study has directly compared apalutamide to LHRH agonists or antagonists in combination with SRT. This trial may be a preamble to the design of a registration trial in such patients or indeed patients with a intermediate and high-risk localized disease that are scheduled for EBRT or brachytherapy as radical treatment and also benefit from 6 months of hormonal treatment.

Radiotherapy Combined With a LHRH (Ant)Agonist Versus Apalutamide in Patients With Biochemical Recurrence After RP

A Phase II Study Comparing Salvage Radiotherapy in Combination With 6 Months of Androgen-deprivation Therapy Versus Anti-androgen Therapy With Apalutamide in Patients With Biochemical Progression After Radical Prostatectomy

EPIC-26 sexual domain score (0 - 100 scale, with higher scores representing better sexual function)

Health related quality of life (QoL) will be assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire designed for patients with prostate cancer. It consists of 27 core items which assess patient function in four domains: physical, social/family, emotional, and functional well-being, which is further supplemented by 12 site specific items to assess for prostate related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score. Higher scores represent better QoL.

Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C30. The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single- item measures. These include five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.

Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) PR25. scale. The EORTC QLQ-PR25 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 25 items specifically related to prostate cancer.

Acute as well as late toxicity will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (published November 27, 2017)

Prostate-specific antigen (PSA) response rates, defined as a decline from baseline in PSA level of 80% or greater, as well as PSA complete response rates, defined as a decline from baseline in PSA level of 90% or greater, will be prospectively collected at 0, 3, 6, and 9 months.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Supportive Therapy in Androgen Deprivation Clinic in Improving Health Outcomes and Managing Side Effects in Patients With Prostate Cancer	NCT02168062	Prostate Adenoc...	Behavioral Diet... Counseling Educational Int... Exercise Interv... Goserelin Aceta... Laboratory Biom... Leuprolide Acet... Quality-of-Life... Triptorelin Pam...	-	University of California, San Francisco
Radiotherapy Combined With a LHRH (Ant)Agonist Versus Apalutamide in Patients With Biochemical Recurrence After RP	NCT03899077	Cancer of Prost...	Apalutamide Leuprorelin Ace... Goserelin Aceta... Triptorelin Pam... Degarelix aceta...	18 Years -	Cancer Research Antwerp
Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer	NCT00194792	Estrogen Recept... HER2-negative B... Progesterone Re... Stage I Breast ... Stage II Breast... Stage IIIA Brea...	exemestane triptorelin pam... capecitabine methotrexate vinorelbine tar... paclitaxel therapeutic con... radiation thera... laboratory biom...	18 Years -	University of Washington
Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer	NCT00194792	Estrogen Recept... HER2-negative B... Progesterone Re... Stage I Breast ... Stage II Breast... Stage IIIA Brea...	exemestane triptorelin pam... capecitabine methotrexate vinorelbine tar... paclitaxel therapeutic con... radiation thera... laboratory biom...	18 Years -	University of Washington
High-Dose Brachytherapy in Treating Patients With Prostate Cancer	NCT02346253	Prostate Adenoc... Stage I Prostat... Stage IIA Prost... Stage IIB Prost... Stage III Prost...	Internal Radiat... Bicalutamide Leuprolide Acet... Goserelin Aceta... Triptorelin Pam... Degarelix Laboratory Biom... Quality-of-Life...	-	Stanford University
Supportive Therapy in Androgen Deprivation Clinic in Improving Health Outcomes and Managing Side Effects in Patients With Prostate Cancer	NCT02168062	Prostate Adenoc...	Behavioral Diet... Counseling Educational Int... Exercise Interv... Goserelin Aceta... Laboratory Biom... Leuprolide Acet... Quality-of-Life... Triptorelin Pam...	-	University of California, San Francisco

Spots Global Cancer Trial Database for triptorelin pamoate