A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance
ENACT
1 other identifier
interventional
227
2 countries
54
Brief Summary
The primary purpose of this study was to compare the time to prostate cancer progression (pathological or therapeutic progression) between patients treated with enzalutamide versus patients undergoing active surveillance.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 prostate-cancer
Started Jun 2016
54 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 29, 2016
CompletedStudy Start
First participant enrolled
June 9, 2016
CompletedFirst Posted
Study publicly available on registry
June 15, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 28, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
August 28, 2020
CompletedResults Posted
Study results publicly available
November 10, 2021
CompletedDecember 6, 2024
November 1, 2024
4.2 years
February 29, 2016
August 27, 2021
November 19, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Prostate Cancer Progression
Time to cancer prostate progression (pathological or therapeutic): time (in months) from date of randomization until the date of cancer progression (pathological or therapeutic). Pathological progression: increase in primary or secondary Gleason pattern by greater than or equal (\>=) 1 or higher proportion of cancer positive cores (\>=15 percent \[%\] increase). Therapeutic progression: earliest occurrence of primary therapy for prostate cancer (prostatectomy/radiation/focal therapy/systemic therapy). Medians and 95% CIs were calculated with the Kaplan-Meier (KM) method. Participants with no cancer progression at the time of study completion, discontinuation or death were censored at the last assessment date. Participants switching therapy during the study were censored at the time of the initial therapy switch, and participants discontinuing therapy were censored at the time of study discontinuation.
From the date of randomization until the date of the cancer progression (pathological or therapeutic) (up to study completion date, 28 Aug 2020; approximately 50 months)
Secondary Outcomes (12)
Number of Participants With Adverse Events (AEs)
From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020; approximately 50 months)
Percentage of Participants Reported Negative Biopsies for Cancer
At the end of months 12 and 24
Change From Baseline in Percent of Cancer Positive Cores at Month 12 and 24
Baseline, months 12 and 24
Time to Prostate-specific Antigen (PSA) Progression
From date of randomization or first dose of enzalutamide until date of PSA progression (pathological or therapeutic) (up to study completion date=28 Aug 2020, median duration: 14.82 months for "Enzalutamide", 8.80 months for "Active Surveillance")
Percentage of Participants With Secondary Rise in Serum PSA
At the end of months 12, 24 and at the end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
- +7 more secondary outcomes
Study Arms (2)
Enzalutamide
ACTIVE COMPARATORParticipants received 160-milligrams (mg) enzalutamide administered as four 40-mg capsules, orally once daily for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow-up period, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Active Surveillance (AS)
OTHERParticipants did not receive any study treatment in this arm but were on continued active surveillance (AS) for 1 year of treatment period. Following the 1-year treatment period, all participants were followed for 1 additional year. Post the 1-year follow up, participants then started the continued follow-up period, in which, participants were followed up every 3 months for these 2 years, after which follow-up was either every 6 months up to 36 months or until the end of study (total duration of follow up in the study was approximately up to 35.9 months).
Interventions
Eligibility Criteria
You may qualify if:
- Histologically proven adenocarcinoma of the prostate diagnosed (with ≥10 core biopsy) within 6 months of screening. The biopsy that was used for this diagnosis must be submitted for central pathology review.
- Prostate cancer categorized (as determined by central pathology review) as low risk is defined as T1c-T2a, PSA\<10, N0, M0 (or presumed N0, M0 if CT/bone scan not done due to low risk of metastases), GS ≤ 6, ECOG status ≤2 and estimated life expectancy \>5 years OR intermediate risk is defined as T2b-T2c, PSA\<20, N0, M0 (or presumed N0, M0 if CT/bone scan not done), GS ≤7 (3+4 pattern only), ECOG status ≤ 2 and estimated life expectancy \> 5 years. Prostate cancer categorized (as determined by central pathology review) to the very low risk category (T1c, GS ≤6, PSA \<10 ng/mL, fewer than 3 prostate biopsy cores positive,
- ≤50% cancer in any core, PSA density \<0.15 ng/mL/g) is not included.
- Ability to swallow study drugs and to comply with study requirements throughout the study
- Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject or legally authorized representative prior to any study-related procedures
- Throughout study, male subject and a female partner who is of childbearing potential must use two acceptable methods of birth control (one of which must include a condom barrier method of contraception) starting at screening and continuing throughout the study period and for three months after the final study drug administration. Two acceptable methods of birth control thus include the following:
- Condom (barrier method of contraception) AND
- One of the following is required:
- i. Established use of oral, injected or implanted hormonal methods of contraception by the female partner; ii. Placement of an intrauterine device or intrauterine system by the female partner; iii. Additional barrier method: Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam / gel / film / cream / suppository by the female partner; iv. Tubal ligation in the female partner.
- Must not donate sperm starting at screening throughout the study period and for 90 days after the final study drug administration.
You may not qualify if:
- Prior radiotherapy, surgery, chemotherapy, or hormonal therapy for prostate cancer
- Very low risk category (T1c, GS ≤6, PSA \<10 ng/mL, fewer than 3 prostate biopsy cores positive, ≤50% cancer in any core, PSA density \<0.15 ng/mL/g)
- Prior transurethral resection of the prostate or prior transurethral microwave thermotherapy of the prostate
- Use of oral glucocorticoids within 1 month of screening
- Use of 5 alpha reductase inhibitor within 1 month of screening or total use, within the last two years prior to screening, of \>3 months
- Presence of metastatic disease
- History of seizure or any condition that may predispose to seizures at any time in the past. History of loss of consciousness or transient ischemic attack within 12 months of screening
- Absolute neutrophil count \< 1,500/μL, platelet count \< 100,000/μL, or hemoglobin \< 6.2 mmol/L (10 g/dL) at screening
- Total bilirubin \>1.5 times the upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2.5 X ULN at screening
- Creatinine \> 177 μmol/L (\> 2 mg/dL) at screening
- Albumin \< 30 g/L (3.0 g/dL) at screening
- Major surgery within 4 weeks prior to Randomization Visit
- Clinically significant cardiovascular disease including:
- Myocardial infarction or uncontrolled angina within 6 months
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (54)
Site US10034
Birmingham, Alabama, 35223, United States
Site US10024
Homewood, Alabama, 35209, United States
Site US10007
Tucson, Arizona, 85704, United States
Site US10055
Tucson, Arizona, 85741, United States
Site US10004
Los Angeles, California, 90048, United States
Site US10026
Sacramento, California, 95670, United States
Site US10010
San Diego, California, 92123, United States
Site US10051
Aurora, Colorado, 80045, United States
Site US10029
Denver, Colorado, 80211, United States
Site US10054
Denver, Colorado, 80220, United States
Site US10072
Bradenton, Florida, 34205, United States
Site US10057
Lakeland, Florida, 33805, United States
Site US10038
Chicago, Illinois, 60611, United States
Site US10062
Chicago, Illinois, 60612, United States
Site US10074
Chicago, Illinois, 60612, United States
Site US10018
Glenview, Illinois, 60026, United States
Site US10071
Lake Barrington, Illinois, 60010, United States
Site US10046
Carmel, Indiana, 46033, United States
Site US10009
Jeffersonville, Indiana, 47130, United States
Site US10037
New Orleans, Louisiana, 70112, United States
Site US10006
Shreveport, Louisiana, 71106, United States
Site US10001
Towson, Maryland, 21204, United States
Site US10032
Boston, Massachusetts, 02111, United States
Site US10008
Troy, Michigan, 48084, United States
Site US10069
Lincoln, Nebraska, 68516, United States
Site US10044
Omaha, Nebraska, 68114, United States
Site US10067
Omaha, Nebraska, 68130, United States
Site US10061
Lebanon, New Hampshire, 03756, United States
Site US10049
Morristown, New Jersey, 07962, United States
Site US10043
Voorhees Township, New Jersey, 08043, United States
Site US10068
Brooklyn, New York, 11215, United States
Site US10050
Cheektowaga, New York, 14225, United States
Site US10030
Garden City, New York, 11530, United States
Site US10028
Poughkeepsie, New York, 12601, United States
Site US10021
Syracuse, New York, 13210, United States
Site US10022
Syracuse, New York, 13210, United States
Site US10047
Gastonia, North Carolina, 28053, United States
Site US10045
Cleveland, Ohio, 44195, United States
Site US10015
Middleburg Heights, Ohio, 44130, United States
Site US10053
Oklahoma City, Oklahoma, 73104, United States
Site US10063
Bala-Cynwyd, Pennsylvania, 19004, United States
Site US10052
Lancaster, Pennsylvania, 17604, United States
Site US10014
Warwick, Rhode Island, 02886, United States
Site US10019
Myrtle Beach, South Carolina, 29572, United States
Site US10011
Nashville, Tennessee, 37209, United States
Site US10056
Dallas, Texas, 75231, United States
Site US10036
Houston, Texas, 77027, United States
Site US10035
San Antonio, Texas, 78229, United States
Site US10058
Richmond, Virginia, 23235, United States
Site US10017
Milwaukee, Wisconsin, 53226, United States
Site CA15005
Abbotsford, British Columbia, V2S 3N6, Canada
Site CA15004
Halifax, Nova Scotia, B3H 2Y9, Canada
Site CA15001
Toronto, Ontario, M4N3M5, Canada
Site CA15003
Toronto, Ontario, M5G2M9, Canada
Related Publications (3)
Handa N, Shore ND, Cooperberg MR, Davicioni E, Zhao X, Elsouda D, Liu Y, Proudfoot JA, Kuperman G, Russell D, Iwata KK, Schaeffer EM, Ross A. Transcriptome profiling of prostatic tumours from ENACT trial patients with or without enzalutamide. BJU Int. 2025 Nov;136(5):920-929. doi: 10.1111/bju.16861. Epub 2025 Jul 31.
PMID: 40742002DERIVEDRoss AE, Iwata KK, Elsouda D, Hairston J, Russell D, Davicioni E, Proudfoot JA, Shore ND, Schaeffer EM. Transcriptome-Based Prognostic and Predictive Biomarker Analysis of ENACT: A Randomized Controlled Trial of Enzalutamide in Men Undergoing Active Surveillance. JCO Precis Oncol. 2024 Apr;8:e2300603. doi: 10.1200/PO.23.00603.
PMID: 38635932DERIVEDShore ND, Renzulli J, Fleshner NE, Hollowell CMP, Vourganti S, Silberstein J, Siddiqui R, Hairston J, Elsouda D, Russell D, Cooperberg MR, Tomlins SA. Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial. JAMA Oncol. 2022 Aug 1;8(8):1128-1136. doi: 10.1001/jamaoncol.2022.1641.
PMID: 35708696DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Global Development, Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Astellas Pharma Global Development, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 29, 2016
First Posted
June 15, 2016
Study Start
June 9, 2016
Primary Completion
August 28, 2020
Study Completion
August 28, 2020
Last Updated
December 6, 2024
Results First Posted
November 10, 2021
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, 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.
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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.