Phase 2
N=90
The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
Prostate Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01790126 ↗Enrolled (actual)
90
Serious AEs
9.0%
Results posted
Mar 2020
Primary outcome: Primary: Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months — -8.04; -6.60; -9.42 Units on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ARN-509 (Drug); LHRH Agonist (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Male
- Sponsor
- Aragon Pharmaceuticals, Inc.
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score at 12 Months |
-8.04; -6.60; -9.42 | — |
| SECONDARY Change From Baseline in FACT-P Total Score at 3 and 24 Months |
-2.62; -4.80; -6.72; -4.43; 1.84; -1.87 | — |
| SECONDARY 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 |
2.80; 3.43; 8.04; 3.49; 4.87; 5.70 | — |
| SECONDARY Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months |
21.74; 3.35; 12.09; 14.31; 15.11; 2.78 | — |
| SECONDARY Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months |
-3.64; -1.80; -3.54; -3.52; -2.91; -3.79 | — |
| SECONDARY Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria |
30.88; 25.79; 36.11 | — |
| SECONDARY Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone |
19.2; 37.0; 37.9 | — |
| SECONDARY Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL |
88.5; 88.9; 96.6 | — |
| SECONDARY Change From Baseline in Body Mass Index (BMI) |
0.00; 0.00; 0.00; -0.02; -0.29; -0.06 | — |
| SECONDARY Change From Baseline in Fasting Plasma Glucose |
-0.07; 0.11; 0.61; 0.19; -0.00; 0.27 | — |
| SECONDARY Change From Baseline in Glycated Hemoglobin (HbA1C) |
0.14; -0.07; 0.06; 0.09; -0.10; 0.08 | — |
| SECONDARY Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides |
0.34; 0.98; 1.28; 0.18; 0.71; 1.35 | — |
| SECONDARY Change From Baseline in Bone Mineral Density (BMD) |
0.00; 0.07; -0.02; 0.00; 0.01; -0.06 | — |
| SECONDARY Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL |
18.89; 18.10; 23.33; 23.98 | — |
| SECONDARY Change From Baseline in Serum Dihydrotestosterone (DHT) Levels |
-0.90; 0.93; -0.90; -0.90; 0.86; -0.90 | — |
| SECONDARY Change From Baseline in Estradiol Levels |
-88.63; 87.87; -94.11; -77.12; 81.29; -103.01 | — |
| SECONDARY Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) |
96.6; 100.0; 100.0 | — |
Summary
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.
Eligibility Criteria
Key Inclusion Criteria
- Histologically proven adenocarcinoma of the prostate
- Rising PSA after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy with curative intent
- PSA doubling time less than or equal to 12 months
- No evidence of metastatic disease on imaging by whole body bone scan and computerized tomography (CT) or Magnetic Resonance Imaging (MRI) of the abdomen/pelvis within 6 weeks prior to randomization
- Minimum PSA 1.0 ng/mL if prior radical prostatectomy +/- adjuvant or salvage radiation; nadir + 2.0 ng/mL if prior RT without prior radical prostatectomy
- Prior androgen deprivation therapy (ADT) allowed if last dose was greater than (>) 6 months prior to randomization
- No prior androgen deprivation therapy (ADT) or anti-androgen for biochemical relapse
- Serum testosterone > 150 ng/dL at study entry
- No history of seizures or medical conditions which may lower seizure threshold
Key Exclusion Criteria
- Use of 5-alpha reductase antagonist (i.e. finasteride, dutasteride) within 6 weeks prior to randomization
- Use of antiandrogen (e.g. flutamide, nilutamide, bicalutamide) within 6 weeks prior to randomization
- Prior bilateral orchiectomy
- Prior treatment with ADT for biochemically relapsed prostate cancer. Prior ADT as neo-adjuvant, concurrent, and/or adjuvant treatment following salvage radiation therapy or prostatectomy for biochemically relapsed disease is allowed provided last dose of ADT is greater than (>) 6 months prior to randomization and the Screening serum testosterone level is greater than or equal to (≥)150 ng/dL
- Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher at randomization
- Any history of seizures or medical condition which lowers seizure threshold
Data sourced from ClinicalTrials.gov (NCT01790126). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.