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NCT01790126

The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer

Completed Phase 2 Results posted Last updated 11 March 2020
What this trial tests

Phase 2 trial testing ARN-509 in Prostate Cancer in 90 participants. Completed in 1 March 2019.

Timeline
4 March 2013
Primary endpoint
1 March 2019
1 March 2019

Quick facts

Lead sponsorAragon Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment90
Start date4 March 2013
Primary completion1 March 2019
Estimated completion1 March 2019
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Aragon Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, male only, with Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months Primary · Baseline, at 12 months

FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48,

GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-8.04± 2.40
Apalutamide-6.60± 2.53
LHRHa + Apalutamide-9.42± 2.30
Change From Baseline in FACT-P Total Score at 3 and 24 Months Secondary · Baseline, at 3 and 24 months

FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACT-General (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48,

Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-2.62± 2.49
Apalutamide-4.80± 2.45
LHRHa + Apalutamide-6.72± 2.29
Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-4.43± 2.91
Apalutamide1.84± 3.17
LHRHa + Apalutamide-1.87± 2.59
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score at 3, 12 and 24 Months Secondary · Baseline, at 3, 12 and 24 months

EORTC QLQ-C30 is a 30 items self-reporting questionnaire resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaire includes 28 items with 4-point Likert type responses from "1-not at all" to "4-very much" to assess functioning and symptoms; 2 items with 7-point Likert scales (1= poor and

Appetite loss: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)2.80± 2.84
Apalutamide3.43± 2.75
LHRHa + Apalutamide8.04± 2.48
Appetite loss: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)3.49± 3.34
Apalutamide4.87± 3.51
LHRHa + Apalutamide5.70± 3.09
Appetite loss: Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-2.29± 4.05
Apalutamide-2.50± 4.35
LHRHa + Apalutamide5.28± 3.29
Cognitive functioning: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-2.44± 3.69
Apalutamide-6.83± 3.62
LHRHa + Apalutamide-7.73± 3.28
Cognitive functioning: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-2.21± 3.40
Apalutamide-11.50± 3.58
LHRHa + Apalutamide-8.27± 3.19
Cognitive functioning: Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-5.08± 4.16
Apalutamide-12.71± 4.64
LHRHa + Apalutamide-4.42± 3.55
Constipation: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)2.90± 3.01
Apalutamide-3.21± 2.94
LHRHa + Apalutamide3.45± 2.65
Constipation: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)10.12± 3.18
Apalutamide0.27± 3.36
LHRHa + Apalutamide7.69± 2.96
Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months Secondary · Baseline, at 3, 12 and 24 months

EORTC QLQ-PR25, a module of the EORTC QLQ-30 questionnaire was used to assess the quality of life. It Consist of 25 questions distributed on 6 domains: urinary symptoms (8 items), incontinence aid (1 item), bowel symptoms (4 items), hormonal treatment-related symptoms (HTRS) (6 items), sexual activity (2 items), and sexual functioning (4 items). Participants answered each of these questions on a 4 point scale (1 'Not at all' to 4 'Very much'). All raw domain scores are linearly transformed to a 0-100 scale, with higher scores reflecting either more symptoms (urinary, bowel, hormonal treatment-

Incontinence aid: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)21.74± 11.72
Apalutamide3.35± 14.22
LHRHa + Apalutamide12.09± 10.97
Incontinence aid: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)14.31± 9.92
Apalutamide15.11± 10.07
LHRHa + Apalutamide2.78± 9.44
Incontinence aid: Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)20.60± 16.04
Apalutamide32.59± 12.52
LHRHa + Apalutamide19.46± 9.82
Bowel symptoms: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)1.43± 1.53
Apalutamide4.27± 1.49
LHRHa + Apalutamide5.37± 1.33
Bowel symptoms: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)5.11± 1.57
Apalutamide1.36± 1.69
LHRHa + Apalutamide3.76± 1.45
Bowel symptoms: Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-0.82± 1.98
Apalutamide0.93± 2.09
LHRHa + Apalutamide1.48± 1.56
HTRS: Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)10.56± 2.25
Apalutamide8.09± 2.21
LHRHa + Apalutamide13.32± 2.01
HTRS: Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)14.72± 2.44
Apalutamide18.05± 2.59
LHRHa + Apalutamide19.43± 2.30
Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months Secondary · Baseline, at 3, 12, 24 months

The SHIM is a well validated abridged 5-item of the 15-item International Index of Erectile Function, which has been extensively studied in men with erectile dysfunction due to various etiologies, including prostate cancer-related therapies. It consists of 5 items pertaining to sexual functioning, with scores ranging from 0-5 for most items. The total score is obtained by adding all five item scores, and can range from 5 to 25. Higher scores indicate higher level of sexual function and less erectile dysfunction.

Change at 3 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-3.64± 0.74
Apalutamide-1.80± 0.67
LHRHa + Apalutamide-3.54± 0.63
Change at 12 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-3.52± 0.81
Apalutamide-2.91± 0.83
LHRHa + Apalutamide-3.79± 0.78
Change at 24 months
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-1.97± 1.16
Apalutamide-2.03± 1.17
LHRHa + Apalutamide-2.39± 0.99
Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria Secondary · Up to 24 months

PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later.

GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)30.8822.54 – NA
Apalutamide25.7920.04 – 38.90
LHRHa + Apalutamide36.1126.97 – 56.64
Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone Secondary · Up to 24 months

Percentage of participants without evidence of PSA or radiographic progression during the 24-month treatment period and with recovery of serum testosterone at 24 months were reported. Testosterone recovery was defined as a serum testosterone greater than (\>) 150 nanogram per deciliter (ng/dL). PSA progression was defined as a rise to greater than 50 percent (%) of the baseline serum PSA or rise of 2 nanogram per milliliter (ng/mL) or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later. Radiographic progression was defined as the detection of new m

GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)19.2
Apalutamide37.0
LHRHa + Apalutamide37.9
Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL Secondary · From 7 to 24 months

Percentage of participants with PSA less than (\<) 0.2 ng/mL after 7 months of protocol therapy were reported.

GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)88.5
Apalutamide88.9
LHRHa + Apalutamide96.6
Change From Baseline in Body Mass Index (BMI) Secondary · Baseline, Day 1 (Cycle 1), Day 28 (Cycle 1, 2, 4, 5, 7, 8, 10 and 11), Day 35 (Cycle 3, 6, 9 and 12) and endpoint (up to 24 months)

Change from baseline in BMI was reported. BMI was calculated as 'body weight in kg/(height in meters)\* (height in meters)'. Endpoint values are from the last measurement within the analysis period.

Change at Cycle 1 Day 1
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.00
LHRHa + Apalutamide0.00
Change at Cycle 1 Day 28
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.00± 0.443
Apalutamide-0.02± 0.569
LHRHa + Apalutamide-0.29± 0.458
Change at Cycle 2 Day 28
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-0.06± 0.903
Apalutamide-0.23± 0.616
LHRHa + Apalutamide-0.32± 0.524
Change at Cycle 3 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.02± 0.837
Apalutamide-0.34± 0.729
LHRHa + Apalutamide-0.24± 0.610
Change at Cycle 4 Day 28
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.19± 0.784
Apalutamide-0.17± 0.710
LHRHa + Apalutamide-0.12± 0.645
Change at Cycle 5 Day 28
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.26± 0.892
Apalutamide-0.15± 0.830
LHRHa + Apalutamide0.05± 0.716
Change at Cycle 6 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.43± 0.851
Apalutamide-0.15± 1.041
LHRHa + Apalutamide-0.01± 0.771
Change at Cycle 7 Day 28
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.48± 0.862
Apalutamide-0.16± 1.114
LHRHa + Apalutamide0.07± 0.743
Change From Baseline in Fasting Plasma Glucose Secondary · Baseline, Day 35 (Cycle 3, 6, 9 and 12)

The change from baseline in fasting plasma glucose levels was analyzed and reported using a mixed-model for repeated measures.

Change at Cycle 3 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-0.07± 0.24
Apalutamide0.11± 0.23
LHRHa + Apalutamide0.61± 0.21
Change at Cycle 6 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.19± 0.19
Apalutamide-0.00± 0.19
LHRHa + Apalutamide0.27± 0.17
Change at Cycle 9 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.10± 0.18
Apalutamide-0.10± 0.19
LHRHa + Apalutamide0.41± 0.16
Change at Cycle 12 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.29± 0.19
Apalutamide0.15± 0.19
LHRHa + Apalutamide0.26± 0.16
Change From Baseline in Glycated Hemoglobin (HbA1C) Secondary · Baseline, Day 35 (Cycle 3, 6, 9 and 12)

The change from baseline in HbA1C was analyzed and reported using a mixed-model for repeated measures.

Change at Cycle 3 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.14± 0.06
Apalutamide-0.07± 0.06
LHRHa + Apalutamide0.06± 0.06
Change at Cycle 6 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.09± 0.06
Apalutamide-0.10± 0.06
LHRHa + Apalutamide0.08± 0.06
Change at Cycle 9 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.16± 0.06
Apalutamide-0.13± 0.06
LHRHa + Apalutamide0.04± 0.06
Change at Cycle 12 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.18± 0.06
Apalutamide-0.09± 0.06
LHRHa + Apalutamide0.13± 0.06
Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides Secondary · Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Change from baseline in cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were analyzed and reported using a mixed-model for repeated measures.

Cholesterol: Change at Cycle 3 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.34± 0.16
Apalutamide0.98± 0.16
LHRHa + Apalutamide1.28± 0.13
Cholesterol: Change at Cycle 6 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.18± 0.16
Apalutamide0.71± 0.16
LHRHa + Apalutamide1.35± 0.13
Cholesterol: Change at Cycle 9 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.24± 0.16
Apalutamide0.66± 0.17
LHRHa + Apalutamide1.21± 0.14
Cholesterol: Change at Cycle 12 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.38± 0.16
Apalutamide0.71± 0.17
LHRHa + Apalutamide0.92± 0.15
LDL Cholesterol: Change at Cycle 3 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.08± 0.15
Apalutamide0.67± 0.15
LHRHa + Apalutamide0.91± 0.13
LDL Cholesterol: Change at Cycle 6 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)-0.03± 0.15
Apalutamide0.36± 0.15
LHRHa + Apalutamide0.87± 0.13
LDL Cholesterol: Change at Cycle 9 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.01± 0.14
Apalutamide0.28± 0.15
LHRHa + Apalutamide0.69± 0.13
LDL Cholesterol: Change at Cycle 12 Day 35
GroupValue95% CI
Luteinizing Hormone Releasing Hormone Agonist (LHRHa)0.07± 0.15
Apalutamide0.31± 0.16
LHRHa + Apalutamide0.57± 0.13

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 6 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Luteinizing Hormone Releasing Hormone Agonist (LHRHa)
Serious: 3/29 (10%)
Deaths: 1/29
Apalutamide
Serious: 0/29 (0%)
Deaths: 0/29
LHRHa + Apalutamide
Serious: 5/31 (16%)
Deaths: 0/31

Serious adverse events (13 terms)

ReactionSystemLuteinizing Hormone Releas…ApalutamideLHRHa + Apalutamide
Acute Myocardial InfarctionCardiac disorders
Angina PectorisCardiac disorders
Atrial FibrillationCardiac disorders
Ventricular TachycardiaCardiac disorders
VertigoEar and labyrinth disorders
Wound InfectionInfections and infestations
Rib FractureInjury, poisoning and procedural complications
Transient Ischaemic AttackNervous system disorders
Device FailureProduct Issues
Pleural EffusionRespiratory, thoracic and mediastinal disorders
AngioedemaSkin and subcutaneous tissue disorders
Toxic Epidermal NecrolysisSkin and subcutaneous tissue disorders
HypertensionVascular disorders
Other adverse events (70 terms — click to expand)

ReactionSystemLuteinizing Hormone Releas…ApalutamideLHRHa + Apalutamide
Hot FlushVascular disorders
FatigueGeneral disorders
GynaecomastiaReproductive system and breast disorders
Nipple PainReproductive system and breast disorders
InsomniaPsychiatric disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
HypercholesterolaemiaMetabolism and nutrition disorders
Back PainMusculoskeletal and connective tissue disorders
Pain in ExtremityMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
HypertensionVascular disorders
Abdominal DiscomfortGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
Abdominal PainGastrointestinal disorders
FlatulenceGastrointestinal disorders
Upper Respiratory Tract InfectionInfections and infestations
FallInjury, poisoning and procedural complications
Decreased AppetiteMetabolism and nutrition disorders
Muscular WeaknessMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
DepressionPsychiatric disorders
Breast TendernessReproductive system and breast disorders
AlopeciaSkin and subcutaneous tissue disorders
TinnitusEar and labyrinth disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
Oedema PeripheralGeneral disorders
Weight IncreasedInvestigations
HypertriglyceridaemiaMetabolism and nutrition disorders
Cognitive DisorderNervous system disorders
Memory ImpairmentNervous system disorders
Libido DecreasedPsychiatric disorders
HaematuriaRenal and urinary disorders
Erectile DysfunctionReproductive system and breast disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Acute Myocardial Infarction, Angina Pectoris, Atrial Fibrillation, Ventricular Tachycardia, Vertigo, Wound Infection, Rib Fracture, Transient Ischaemic Attack.

Data from ClinicalTrials.gov NCT01790126 adverse events section.

Sponsor's own description

The proposed clinical trial will study the effects of 12 months of therapy with ARN-509 alone, or in combination with an LHRH agonist (LHRHa), each compared with LHRHa alone, in men with a rapidly rising serum PSA after prior definitive local therapy for prostate cancer. The endpoints selected reflect measurable short term effects of androgen deprivation therapy (ADT), including quality of life and several metabolic parameters. In addition, the relative effect of each treatment strategy on PSA suppression as well as testosterone recovery (and subsequent PSA progression) after 12 months of therapy will be evaluated.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting signaling pathways in prostate cancer: mechanisms and clinical trials.
    He Y, Xu W, Xiao YT, Huang H, et al · · 2022 · cited 192× · PMID 35750683 · DOI 10.1038/s41392-022-01042-7
  2. The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches.
    Alarcón-Zendejas AP, Scavuzzo A, Jiménez-Ríos MA, Álvarez-Gómez RM, et al · · 2022 · cited 60× · PMID 35422101 · DOI 10.1038/s41391-022-00537-2
  3. Castration-resistant prostate cancer: latest evidence and therapeutic implications.
    Suzman DL, Antonarakis ES. · · 2014 · cited 59× · PMID 25057303 · DOI 10.1177/1758834014529176
  4. Recent progress in pharmaceutical therapies for castration-resistant prostate cancer.
    Yin L, Hu Q, Hartmann RW. · · 2013 · cited 35× · PMID 23880851 · DOI 10.3390/ijms140713958
  5. Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer.
    Aggarwal R, Alumkal JJ, Szmulewitz RZ, Higano CS, et al · · 2022 · cited 16× · PMID 36212187 · DOI 10.1155/2022/5454727
  6. Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis.
    Matsukawa A, Yanagisawa T, Fazekas T, Miszczyk M, et al · · 2025 · cited 7× · PMID 39266730 · DOI 10.1038/s41391-024-00890-4
  7. Interactions between key genes and pathways in prostate cancer progression and therapy resistance.
    Wu F, Zhang H, Hao M. · · 2025 · cited 4× · PMID 39917165 · DOI 10.3389/fonc.2025.1467540
  8. Incidence, Management, and Prevention of Gynecomastia and Breast Pain in Patients with Prostate Cancer Undergoing Antiandrogen Therapy: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
    Tsuboi I, Schulz RJ, Laukhtina E, Wada K, et al · · 2025 · cited 3× · PMID 39935942 · DOI 10.1016/j.euros.2025.01.001

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