Safety and Efficacy of TAK-385 for Patients With Localized Prostate Cancer
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase 2, Randomized, Open-Label, Parallel Group Study Evaluating the Safety and Efficacy of TAK-385, an Oral Gonadotropin-Releasing Hormone (GnRH) Antagonist, for Patients With Localized Prostate Cancer Requiring Neoadjuvant and Adjuvant Androgen Deprivation Therapy With External Beam Radiation Therapy (EBRT)|
- Percentage of Participants With Effective Castration Rate Over 25 Weeks [ Time Frame: Day 1 Week 5 up to Day 1 Week 25 ]Castration rate is defined as the observed percentage of participants who have testosterone concentrations less than (<) 50 nanogram per deciliter (ng/dL) (1.73 nanomole per liter [nmol/L]) at all scheduled visits.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs [ Time Frame: Baseline up to Week 29 ]
- Number of Participants With TEAEs Related to Physical Findings [ Time Frame: Baseline up to Week 29 ]
- Number of Participants With TEAEs Related to 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Baseline up to Week 29 ]
- Number of Participants With TEAEs Categorized Into Investigations Related to Chemistry, Hematology or Urinalysis [ Time Frame: Baseline up to Week 29 ]
- Number of Participants Reporting One or More TEAEs and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 29 ]
- Average Percent Change in Prostate Size [ Time Frame: Baseline, Day 1 Week 9 to Day 1 Week 13 ]Percent change in prostate size was assessed at a follow up visit between Day 1 Week 9 to Day 1 Week 13.
- Time to Achieve Effective Castration [ Time Frame: Baseline up to Week 37 ]Time to effective castration is defined as days from first dose to first testosterone measurement that is <50 ng/dL.
- Time to Achieve Profound Castration [ Time Frame: Baseline up to Week 37 ]Time to profound castration is defined as days from first dose to first testosterone measurement that is <20 ng/dL.
- Estimated Time to Testosterone Recovery (TTR) [ Time Frame: Up to Day 1 Week 37 ]TTR is defined as the time from 1 day after the last dose of TAK-385 or 4 weeks plus 1 day after the last dose of degarelix to testosterone recovery. Testosterone recovery is defined as back to baseline or >280 ng/dL whichever occurs first. TTR was determined during 12 weeks after the discontinuation of androgen deprivation therapy (ADT).
- Percentage of Participants Who Have Recovered to Baseline Value of Testosterone [ Time Frame: Up to Day 1 Week 37 ]
- Percentage of Participants Who Have Recovered to >280 ng/dL Testosterone [ Time Frame: Day 1 Week 25 up to Day 1 Week 37 ]
- Number of Participants With PSA Response of >=50% and >=90% Reduction [ Time Frame: Day 1 Week 13 ]Prostate-specific Antigen (PSA) response was defined as 50% and 90% reduction from baseline in serum PSA levels.
- Percent Change From Baseline in Serum PSA Concentration [ Time Frame: Baseline, Day 1 of Week 2, 3 , 5, 9, 13, 17, 21, 25, 29, 33 and 37 ]
- PSA Nadir [ Time Frame: Baseline up to Day 1 Week 25 ]
- Serum PSA Concentration [ Time Frame: Day 1 of Week 13, 25, 29, 33 and 37 ]
- Plasma Concentrations of TAK-385 [ Time Frame: Day 1 Week 1, 2, 3, 5, 9, 13, 17, 25, 33, 37: Pre-dose; Day 1 Week 5, 13: 2 hrs Post-dose; Day 4 Week 1: Pre-dose ]
- Serum Luteinizing Hormone (LH) Level [ Time Frame: Baseline, Day 1 of Weeks 2, 3, 5, 9, 13, 17, 21, 25, 29, and 37 ]
- Serum Follicle-Stimulating Hormone (FSH) Level [ Time Frame: Baseline, Day 1 of Week 2, 5, 13, 25 and 29 ]
- Serum Sex Hormone-Binding Globulin (SHBG) Level [ Time Frame: Baseline, Day 1 of Week 2, 5, 13, 25 and 29 ]
- Percent Change From Baseline in Aging Male's Symptoms (AMS) Total Scale Score [ Time Frame: Day 1 of Weeks 5, 13, 25, 29, 33 and 37 ]AMS scale is a self-administered questionnaire used to 1) assess symptoms of aging (independent from those that are disease related) between groups of males under different conditions; 2) evaluate the severity of symptoms over time; and 3) measure changes before and after androgen therapy. Each question was answered between none (1) to extremely severe (5) for 17 items from psychological (5 items), somatic (7 items), and sexual (5 items) categories. Total score is sum of all the item scores and range from 17 (minimum) to 85 (maximum), where high score indicated high level of symptoms.
- Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Score [ Time Frame: Baseline and last post-baseline value up to Week 37 ]EORTC QLQ-C30 included 30 questions comprising 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, nausea/vomiting), single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties) and a global health and QOL scale. Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'Very poor' to 7 'Excellent'). All domain scores were calculated as an average of item scores and transformed to 0-100 score range where a high score from 0-100 indicates: A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status/quality of life (QoL) represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problem.
- Change From Baseline in 25-item Prostate Cancer-specific Questionnaire Supplement (EORTC QLQ-PR25) Score [ Time Frame: Baseline and last post-baseline value up to Week 37 ]EORTC QLQ-PR25 : EORTC module designed to supplement the QLQ-C30 for any application in prostate cancer. 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). Questions used 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).
|Study Start Date:||June 2014|
|Study Completion Date:||December 2015|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
TAK-385 320 mg, tablets, orally, once, on Day 1, followed by TAK-385 120 mg, orally, once daily for 24 weeks. Each participant may have one upward dose adjustment of 40 mg for efficacy and/or one downward dose adjustment of 40 mg for safety during the study.
Active Comparator: Degarelix
Degarelix 240 mg, injection, subcutaneous, on Day 1, followed by degarelix 80 mg, injection, subcutaneous, once every four weeks, for 24 weeks.
Other Name: Firmagon®
The drug being tested in this study is called TAK-385. Men with prostate cancer benefit from receiving androgen deprivation therapy (ADT) to minimize testosterone levels before, during and after EBRT. This combination increases the potential success of treating their disease. This study will see if TAK-385 [an oral gonadotropin-releasing hormone (GnRH) antagonist] brings testosterone levels down sufficiently, with the convenience and comfort of taking a pill. It will look at the time it takes to restore testosterone levels after radiation therapy as well. One hundred participants will be assigned by chance (like flipping a coin) to a treatment group: 60 to TAK-385, and 40 to degarelix.
Those assigned to TAK-385 will take a daily pill. Those assigned to degarelix will receive an injection under the skin once every four weeks at the clinic. They will start radiation therapy when testosterone is low enough, after at least 12 weeks of treatment. This trial will be conducted at clinics in the United States (US) and United Kingdom (UK). Participants will visit the clinic up to 14 times over 37 weeks for physical exams and blood tests, and might receive one follow-up telephone call.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02135445
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|Study Director:||Medical Monitor||Millennium Pharmaceuticals, Inc.|