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

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: ARN-509; Drug: LHRH Agonist	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	90 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	The Role of Highly Selective Androgen Receptor (AR) Targeted Therapy in Men With Biochemically Relapsed Hormone Sensitive Prostate Cancer
Actual Study Start Date :	March 4, 2013
Estimated Primary Completion Date :	December 31, 2019
Estimated Study Completion Date :	December 31, 2019

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: ARN-509; ARN-509 Tablets, 240 mg/day administered orally	Drug: ARN-509
Active Comparator: LHRH agonist + ARN-509; Choice of LHRHa per investigator discretion/site practice guidelines (e.g, Eligard®, Zoladex®, Lupron Depot®, Trelstar®) and ARN-509 Tablets, 240 mg/day administered orally	Drug: ARN-509 Drug: LHRH Agonist; Other Names: Eligard®; Lupron Depot®; Zoladex®; Trelstar®
Active Comparator: LHRH agonist; Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).	Drug: LHRH Agonist; Other Names: Eligard®; Lupron Depot®; Zoladex®; Trelstar®

Outcome Measures

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Primary Outcome Measures :

1. Mean Change From Baseline in Total Functional Assessment of Cancer Therapy - Prostate (FACT-P) Score [ Time Frame: 12 months ]
   FACT-P includes a 27-item "core" quality of life measure (FACT-G) grouped into 4 sub-scales: physical, social/family, emotional, and functional well-being. The prostate cancer-specific subscale contains an additional 12 items; 10 of which are prostate cancer specific physical problems. Items are rated on a 5-item Likert scale, from 0, "not at all", to 4, "very much". Total range of scores is from 0 - 156. Higher scores indicate higher degree of functioning and better quality of life.

Secondary Outcome Measures :

1. Time to Prostate-Specific Antigen (PSA) progression [ Time Frame: 7-24 months ]
   PSA progression will be defined as a rise to greater than 50% of the baseline serum PSA or rise of 2 ng/mL or more above the nadir, whichever is higher, confirmed by repeat measurement at least 2 weeks later.
2. Percentage of Participants without PSA or radiographic progression and recovery of serum testosterone [ Time Frame: 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. Testosterone recovery will be defined as a serum testosterone > 150 ng/dL.
3. Percentage of Participants with a serum PSA < 0.2 nanogram/milliliter (ng/mL) [ Time Frame: Month 7 ]
4. Mean change from baseline in body mass index over time [ Time Frame: Baseline up to Month 24 ]
   Body Mass Index (BMI) is calculated by dividing the body weight (in kilogram) by the square of height (in meters).
5. Mean change from baseline in Fasting Palsma Glucose over time [ Time Frame: Baseline up to Month 24 ]
6. Mean change from Baseline in Fasting Plasma Insulin over time [ Time Frame: Baseline up to Month 24 ]
7. Mean change from Baseline in hemoglobin A1C (HbA1C) over time [ Time Frame: Baseline up to Month 24 ]
8. Mean change from Baseline in Fasting Lipid Profile over time [ Time Frame: Baseline up to Month 24 ]
9. Mean change from Baseline in bone mineral density over time [ Time Frame: Baseline up to Month 24 ]
   Bone mineral density will be measured at the femoral neck, and lumbar spine by DEXA.
10. Mean change from Baseline in serum dihydrotestosterone (DHT) levels over time [ Time Frame: Baseline up to Month 24 ]
11. Mean change from Baseline in estradiol levels over time [ Time Frame: Baseline up to Month 24 ]
12. Number of participants with adverse events [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ]
    An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
13. Number of participants with abnormal findings in physical exams [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ]
14. Number of participants with abnormal findings in laboratory tests [ Time Frame: From signing of informed consent form up to 30 days after the last dose of study medication ]
15. Percentage of Participants emerging with ARF876L mutation at the end of treatment and progression [ Time Frame: up to 24 months ]
16. Percentage of Participants expressing RNA markers previously demonstrated to confer resistance ARN509 at Baseline, end of treatment and progression [ Time Frame: up to 24 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

United States, Arizona
Scottsdale, Arizona, United States
United States, California
San Francisco, California, United States
United States, Illinois
Chicago, Illinois, United States
United States, Oregon
Portland, Oregon, United States
United States, Washington
Seattle, Washington, United States

Sponsors and Collaborators

Aragon Pharmaceuticals, Inc.

Investigators

Study Director:	Aragon Pharmaceuticals, Inc Clinical Trial	Aragon Pharmaceuticals, Inc.

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01790126 History of Changes
Other Study ID Numbers:	CR103305; ARN-509-002
First Posted:	February 13, 2013
Last Update Posted:	April 6, 2018
Last Verified:	April 2018

Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Aragon Pharmaceuticals, Inc.:

Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Hypersensitivity; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Immune System Diseases; Hormones; Androgens; Leuprolide	Goserelin; Triptorelin Pamoate; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents