February 5, 2016
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February 9, 2016
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January 8, 2020
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January 21, 2020
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April 19, 2024
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March 9, 2016
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October 14, 2018 (Final data collection date for primary outcome measure)
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- Radiographic Progression-Free Survival (rPFS) Based on Independent Central Review (ICR) of Bone Scan According to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) Criteria [ Time Frame: From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline or week 13 according to PCWG2 criteria, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.
- rPFS Based on ICR of Bone Scan According to Protocol Assessment Criteria [ Time Frame: From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months. ]
rPFS was calculated as the time from the date of randomization to the first objective evidence of radiographic progression disease (rPD) at any time or death up to 24 weeks after study drug discontinuation without documented radiographic progression, whichever occurred first. rPD was defined as progressive disease by Response Evaluation Criteria in Solid Tumors version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan compared to baseline for week 13 or the best response on treatment for week 25 or later assessments, as assessed by ICR or death. In participants with no rPFS event, rPFS was censored on the date of last evaluable radiographic assessment prior to the data analysis cutoff date. In participants with no baseline radiographic assessment, participants with no postbaseline radiographic assessments and participants with all postbaseline radiographic assessments documented as "not evaluable (NE)," rPFS was censored on the date of randomization.
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Radiographic progression-free survival (rPFS) [ Time Frame: Up to 4 years ] Defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review or death (defined as death from any cause within 24 weeks from study drug discontinuation), whichever comes first.
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- Overall Survival (OS) [ Time Frame: From date of randomization to OS final analysis (28 May 2021); Maximum treatment duration was 58.6 months ]
OS was defined as the time from randomization to death due to any cause. In participants still alive at the date of the analysis cutoff point, OS was censored on the last date the participant was known to be alive. OS was analyzed using Kaplan-Meier estimates.
- Time to Prostate Specific Antigen (PSA) Progression [ Time Frame: From randomization until the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. A PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir, which was confirmed by a second consecutive value at least 3 weeks later. In participants with no PSA progression, time to PSA progression was censored on the date of the last PSA sample taken (or last value prior to 2 or more consecutive missed PSA assessments).
- Time to Start of New Antineoplastic Therapy [ Time Frame: From date of randomization to data cut-off date (28 May 2021); Maximum treatment duration was 58.6 months ]
In participants with a new antineoplastic therapy initiated for prostate cancer after randomization, time to start of a new antineoplastic therapy was defined as the time interval from randomization to the date of the first dose administration of the first antineoplastic therapy. In participants with no new antineoplastic therapy initiated for prostate cancer after randomization, time to start of new antineoplastic therapy was censored on the last visit date or the date of randomization, whichever occurred last. Time to start of new antineoplastic therapy was analyzed using Kaplan-Meier estimates.
- PSA Undetectable Rate [ Time Frame: Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
The PSA undetectable rate was defined as the percentage of participants with undetectable (< 0.2 ng/mL) PSA values at any time during study treatment, of those participants with detectable (≥ 0.2 ng/mL) PSA values at baseline.
- Objective Response Rate (ORR) [ Time Frame: Up to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
The ORR was calculated as the percentage of participants who achieved a completed response (CR) or a partial response (PR) (unconfirmed responses) in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by ICR.
- Time to Deterioration in Urinary Symptoms [ Time Frame: From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
In participants with deterioration, the time to deterioration was calculated as the time interval between randomization and the first deterioration in urinary symptoms at any postbaseline visit. A deterioration in urinary symptoms was defined as an increase in the Quality of Life Prostate-specific Questionnaire (QLQ-PR25) modified urinary symptoms. Subscale score by ≥ 50% of the standard deviation observed in the QLQ-PR25 modified urinary symptoms subscale score at baseline. Modified urinary symptoms subscale score consisted of 3-items (Q31 - Q33) from the QLQ-PR25, each scored from 1 (not at all) to 4 (very much). The total modified urinary symptoms subscale score ranges from 0-100, with higher scores represents a higher level of symptomatology/problems. In participants without deterioration in urinary symptoms, the time to deterioration in urinary symptoms was censored on the date the last urinary symptoms QLQ-PR25 score was calculable.
- Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
Time to first SSE was calculated as the time from randomization to the occurrence of the first SSE prior to the data analysis cut-off date. An SSE was defined as radiation to bone, surgery to bone, clinically apparent pathological bone fracture, or spinal cord compression. In participants with no SSE by the time of the data cut-off point, time to SSE was censored on the last visit date or the date of randomization, whichever occurred last.
- Time to Castration Resistance [ Time Frame: From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
Time to castration resistance was calculated as the time from randomization to the first castration-resistant event. A castration resistance event was defined as any of the following in the presence of castrate levels of testosterone (< 50 ng/dL): radiographic disease progression, PSA progression or SSE, whichever occurred first. In participants with no documented castration resistance event, the time to castration resistance was censored on the latest date from: the date of last radiologic assessment, the last PSA sample taken prior to the start of any new prostate cancer therapy and prior to 2 or more consecutive missed PSA assessments (if applicable), and the last visit date performed.
- Time to Deterioration of Quality of Life (QoL) in Functional Assessment of Cancer Therapy-Prostate (FACT-P) [ Time Frame: From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
Time to deterioration of QoL was calculated as the time interval from the date of randomization to the first date a decline from baseline of 10 points or more in the FACT-P total score was recorded. The FACT-P consists of 27 core items that assess participant function in 4 domains and 12 prostate cancer-related items grouped into 5 subscales as follows: physical wellbeing, social/family wellbeing, emotional wellbeing, functional wellbeing and prostate cancer subscale. Each item is rated on a 0 to 4 Likert-type scale. The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0 to 156), where high score represent better quality of life. In participants without FACT-P progression, the time to deterioration of QoL was censored on the date of the last FACT-P total score was calculable.
- Time to Pain Progression Based on Brief Pain Inventory-Short Form (BPI-SF) [ Time Frame: From randomization to the data cut-off date of 14 October 2018; maximum duration of treatment was 26.6 months ]
Time to pain progression was defined as time from randomization to the first pain progression event. Pain progression was defined as an increase of ≥ 30% from baseline in the average BPI-SF pain severity score. BPI-SF contains 9 questions with rating scales from 0 (no pain/no interference) to 10 (worst pain/interferes completely). Total score was calculated as the average of each question. Higher scores represent a higher level of pain or interference. In participants with no pain progression event, time to pain progression was censored on the last visit date where BPI-SF was collected.
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- Overall survival (OS) [ Time Frame: Up to 7 years ]
Defined as the time from randomization to death from any cause.
- Time to first symptomatic skeletal event (SSE) [ Time Frame: Up to 4 years ]
Defined as the time from randomization to the occurrence of the first SSE. SSE is defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression.
- Time to castration resistance [ Time Frame: Up to 4 years ]
Defined as the time from randomization to the first castration-resistant event (radiographic disease progression, prostate-specific antigen (PSA) progression or SSE), whichever occurs first.
- Time to deterioration of quality of life (QoL) [ Time Frame: Up to 4 years ]
Defined as time from randomization to a 10-point reduction of the Functional Assessment of Cancer Therapy - Prostate (FACT-P) total score
- Time to initiation of a new antineoplastic therapy [ Time Frame: Up to 4 years ]
Defined as time from randomization to the initiation of antineoplastic subsequent to the study treatments.
- Time to PSA progression [ Time Frame: Up to 4 years ]
PSA progression is defined as a ≥ 2 µg/L (2 ng/mL) above the nadir.
- PSA undetectable rate [ Time Frame: Up to 4 years ]
Defined as percentage of subjects with detectable (< 0.2 ng/mL) during study treatment.
- Objective response rate [ Time Frame: Up to 4 years ]
Defined as the percentage of subjects with measureable disease at baseline who achieved a complete or partial response in their soft tissue disease using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
- Time to pain progression [ Time Frame: Up to 4 years ]
Defined as time from randomization to an increase of 30% in pain severity score from baseline using the Brief Pain Inventory-Short Form (BPI-SF)
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Not Provided
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Not Provided
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A Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
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A Multinational, Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)
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The purpose of this study was to evaluate the efficacy of enzalutamide plus androgen deprivation therapy (ADT) as measured by radiographic progression-free survival (rPFS) based on central review. The study also evaluated the safety of enzalutamide plus ADT in mHSPC.
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Following unblinding at the end of the double-blind period and demonstration of a statistically significant advantage of enzalutamide over placebo when added to ADT as assessed by the primary endpoint of rPFS, subjects were eligible to transition to an open-label portion of the study.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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Metastatic Hormone Sensitive Prostate Cancer
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- Drug: Enzalutamide
Oral
Other Name: Xtandi
- Drug: Placebo
Oral
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- Experimental: Enzalutamide + Androgen Deprivation Therapy (ADT)
Participants received 160 mg enzalutamide orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. Eligible participants who received enzalutamide during double-blind treatment period and provided informed consent to take part in open-label period continued to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or Luteinizing hormone-releasing hormone (LHRH) agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Intervention: Drug: Enzalutamide
- Placebo Comparator: Placebo + Androgen Deprivation Therapy (ADT)
Participants received matching placebo orally once daily during double-blind treatment period until radiographic progression was documented or until the participants started an investigational agent or new therapy for treatment of prostate cancer or until any other discontinuation criterion was met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Intervention: Drug: Placebo
- Experimental: Placebo followed by Enzalutamide
Eligible participants who received enzalutamide matching placebo during double-blind treatment period and provided informed consent to take part in open-label period switched to receive 160 mg enzalutamide orally once daily in open-label period until disease progression, unacceptable toxicity or any other discontinuation criteria were met. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment as per standard of care and provided by the site's pharmacy stock.
Intervention: Drug: Enzalutamide
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- Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. doi: 10.1200/JCO.19.00799. Epub 2019 Jul 22.
- Cella D, Ganguli A, Turnbull J, Rohay J, Morlock R. US Population Reference Values for Health-Related Quality of Life Questionnaires Based on Demographics of Patients with Prostate Cancer. Adv Ther. 2022 Aug;39(8):3696-3710. doi: 10.1007/s12325-022-02204-3. Epub 2022 Jun 22.
- Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore ND, Gomez-Veiga F, Rosbrook B, Zohren F, Yamada S, Haas GP, Stenzl A. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022 May 20;40(15):1616-1622. doi: 10.1200/JCO.22.00193. Epub 2022 Apr 14.
- Stenzl A, Dunshee C, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, Flaig TW, Tombal B, Morlock R, Ivanescu C, Ramaswamy K, Saad F, Armstrong AJ. Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study. Eur Urol. 2020 Oct;78(4):603-614. doi: 10.1016/j.eururo.2020.03.019. Epub 2020 Apr 23.
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Active, not recruiting
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1150
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1100
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July 31, 2024
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October 14, 2018 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
- Subject is considered an adult according to local regulation at the time of signing informed consent.
- Subject is diagnosed with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet cell or small cell histology.
- Subject has metastatic prostate cancer documented by positive bone scan (for bone disease) or metastatic lesions on computed tomography (CT) or magnetic resonance imaging (MRI) scan (for soft tissue). Subjects whose disease spread is limited to regional pelvic lymph nodes are not eligible.
- Once randomized at day 1, subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Inclusion Criteria for Open-Label Extension:
- Subject received randomized double-blind treatment in ARCHES
- Subject has not met any of the discontinuation criteria in the main ARCHES protocol
- Subject is willing to maintain ADT with LHRH agonist or antagonist or has had a bilateral orchiectomy.
- Subject is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study
- Subject and subject's female partner agree to follow contraception and sperm donation requirements in main protocol
Exclusion Criteria:
Exclusion Criteria for Open-Label Extension:
- Subject has taken commercially available enzalutamide (Xtandi).
- Subject's disease has progressed radiographically during the double-blind period of the study and treatment with study drug was stopped prior to study-wide unblinding. (Note: Subjects who progressed radiographically while in the double-blind portion of the study and continued treatment per protocol are allowed to participate in the open label extension.)
- After study-wide unblinding, subject has started any new investigational agent or anti-neoplastic therapy intended to treat prostate cancer
- Subject has any clinically significant disorder or condition including excessive alcohol or drug abuse, or secondary malignancy, which may interfere with study participation
- Subject has current or previously treated brain metastasis or active leptomeningeal disease
- Subject has a history of seizure or any condition that may increase the risk of seizure
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Sexes Eligible for Study: |
Male |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Argentina, Australia, Belgium, Canada, Chile, Denmark, Finland, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, United Kingdom, United States
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NCT02677896
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9785-CL-0335 2015-003869-28 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com. |
Supporting Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Clinical Study Report (CSR) |
Time Frame: |
Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data. |
Access Criteria: |
Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement. |
URL: |
https://www.clinicalstudydatarequest.com/ |
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Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
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Same as current
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Astellas Pharma Global Development, Inc.
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Same as current
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Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
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Study Director: |
Medical Director |
Astellas Pharma Global Development, Inc. |
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Astellas Pharma Inc
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April 2024
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