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

Primary Purpose

Prostate Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

ARN-509

LHRH Agonist

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Arm Label

ARN-509

LHRH agonist + ARN-509

LHRH agonist

Arm Description

ARN-509 Tablets, 240 mg/day administered orally

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

Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).

Outcomes

Primary Outcome Measures

Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Total Score 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, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.

Secondary Outcome Measures

Change From Baseline in FACT-P Total Score at 3 and 24 Months

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

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 7= excellent) for global health and overall health related quality of life. Scores are transformed to 0 to 100 scale, with higher scores representing better GHS, better functioning, and more symptoms.

Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score 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-related symptoms) or higher levels of activity or functioning (sexual).

Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score 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.

Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria

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.

Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone

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 metastasis on either bone scan or cross-sectional imaging (computed tomography [CT] or magnetic resonance imaging [MRI]).

Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL

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

Change From Baseline in Body Mass Index (BMI)

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 From Baseline in Fasting Plasma Glucose

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

Change From Baseline in Glycated Hemoglobin (HbA1C)

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

Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides

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

Change From Baseline in Bone Mineral Density (BMD)

Change from baseline in BMD was assessed for femoral neck and lumber spine with DEXA scans.

Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL

The time to serum testosterone recovery to > 50 ng/dL and > 150 ng/dL from Month 13 to Month 24 of protocol therapy was reported.

Change From Baseline in Serum Dihydrotestosterone (DHT) Levels

Change from baseline in serum DHT levels was reported.

Change From Baseline in Estradiol Levels

Change from baseline in estradiol levels was reported.

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. Treatment-emergent adverse events are those that occurred between the date of 1st dose of study drug and date of last dose of study drug plus 30 days.

Full Information

NCT ID

NCT01790126

First Posted

February 8, 2013

Last Updated

February 27, 2020

Sponsor

Aragon Pharmaceuticals, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01790126

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

March 4, 2013 (Actual)

Primary Completion Date

March 1, 2019 (Actual)

Study Completion Date

March 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aragon Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Men with Biochemically Relapsed Hormone Sensitive Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

90 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ARN-509

Arm Type

Active Comparator

Arm Description

ARN-509 Tablets, 240 mg/day administered orally

Arm Title

LHRH agonist + ARN-509

Arm Type

Active Comparator

Arm Description

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

Arm Title

LHRH agonist

Arm Type

Active Comparator

Arm Description

Choice of LHRHa per investigator discretion/site practice guidelines (e.g., Eligard®, Zoladex®, Lupron Depot®, Trelstar®).

Intervention Type

Drug

Intervention Name(s)

ARN-509

Intervention Type

Drug

Intervention Name(s)

LHRH Agonist

Other Intervention Name(s)

Eligard®, Lupron Depot®, Zoladex®, Trelstar®

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, at 12 months

Secondary Outcome Measure Information:

Title

Change From Baseline in FACT-P Total Score at 3 and 24 Months

Description

Time Frame

Baseline, at 3 and 24 months

Title

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

Description

Time Frame

Baseline, at 3, 12 and 24 months

Title

Change From Baseline in EORTC Quality of Life Questionnaire-Prostate 25 (QLQ-PR25) Score at 3, 12 and 24 Months

Description

Time Frame

Baseline, at 3, 12 and 24 months

Title

Change From Baseline in Sexual Health Inventory for Men (SHIM) Total Score at 3, 12, 24 Months

Description

Time Frame

Baseline, at 3, 12, 24 months

Title

Time to Prostate Specific Antigen (PSA) Progression Based on Modified Prostate Cancer Clinical Trials Working Group (PCWG2) Criteria

Description

Time Frame

Up to 24 months

Title

Percentage of Participants Without PSA or Radiographic Progression and With Recovery of Serum Testosterone

Description

Time Frame

Up to 24 months

Title

Percentage of Participants With a Serum PSA Less Than 0.2 ng/mL

Description

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

Time Frame

From 7 to 24 months

Title

Change From Baseline in Body Mass Index (BMI)

Description

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.

Time Frame

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)

Title

Change From Baseline in Fasting Plasma Glucose

Description

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

Time Frame

Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Title

Change From Baseline in Glycated Hemoglobin (HbA1C)

Description

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

Time Frame

Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Title

Change From Baseline in Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and Triglycerides

Description

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

Time Frame

Baseline, Day 35 (Cycle 3, 6, 9 and 12)

Title

Change From Baseline in Bone Mineral Density (BMD)

Description

Change from baseline in BMD was assessed for femoral neck and lumber spine with DEXA scans.

Time Frame

Baseline, Cycle 12 Day 35

Title

Median Time to Serum Testosterone Recovery to Greater Than (>) 50 ng/dL (Non-castrate) and > 150 ng/dL

Description

The time to serum testosterone recovery to > 50 ng/dL and > 150 ng/dL from Month 13 to Month 24 of protocol therapy was reported.

Time Frame

Month 13 to Month 24

Title

Change From Baseline in Serum Dihydrotestosterone (DHT) Levels

Description

Change from baseline in serum DHT levels was reported.

Time Frame

Baseline, Day 35 (Cycle 6 and Cycle 12)

Title

Change From Baseline in Estradiol Levels

Description

Change from baseline in estradiol levels was reported.

Time Frame

Baseline, Day 35 (Cycle 6 and Cycle 12)

Title

Percentage of Participants With Treatment Emergent Adverse Events (TEAEs)

Description

Time Frame

From date of 1st dose of study drug to date of last dose of study drug plus 30 days (up to 6 years)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Aragon Pharmaceuticals, Inc Clinical Trial

Organizational Affiliation

Aragon Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

City

Scottsdale

State/Province

Arizona

Country

United States

City

San Francisco

State/Province

California

Country

United States

City

Chicago

State/Province

Illinois

Country

United States

City

Portland

State/Province

Oregon

Country

United States

City

Seattle

State/Province

Washington

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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