A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance

NCT ID: NCT02799745

Last Updated: 2024-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 227 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-09
• Study Completion Date: 2020-08-28

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.

Detailed Description

This was a multicenter, randomized, open label exploratory study, conducted in the US and Canada, evaluating the efficacy and safety of enzalutamide for extension of time to prostate cancer progression (pathological or therapeutic) in patients with clinically localized, histologically proven prostate cancer that is categorized as low risk or intermediate risk and who were under AS.

Conditions

Prostate Cancer

Keywords

Therapeutic Cancer Progression; Pathological Cancer Progression; Enzalutamide; Prostate Cancer; Active surveillance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Enzalutamide

Participants 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).

Group Type: ACTIVE_COMPARATOR

Enzalutamide

Intervention Type: DRUG

Oral

Active Surveillance (AS)

Participants 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).

Group Type: OTHER

Active Surveillance

Intervention Type: OTHER

Interventions

Enzalutamide

Oral

Intervention Type: DRUG

Active Surveillance

Intervention Type: OTHER

Other Intervention Names

MDV3100; Xtandi

Eligibility Criteria

Inclusion Criteria

• 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:

1. Condom (barrier method of contraception) AND

2. 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.

Exclusion Criteria

• 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:

1. Myocardial infarction or uncontrolled angina within 6 months

2. Congestive heart failure New York Heart Association (NYHA) class 3 or 4

3. History of clinically significant ventricular arrhythmias

4. History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place

5. Hypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening

6. Bradycardia as indicated by a heart rate of < 45 beats per minute on the screening electrocardiogram (ECG) and on physical examination

7. Uncontrolled hypertension as indicated by at least 2 consecutive measurements of a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the Screening Visit

• Known hypersensitivity to enzalutamide or any of its components.
• Subject has received investigational therapy within 28 days or 5 half lives, whichever is longer, prior to screening

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

INDUSTRY

Sponsor Role: collaborator

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Site US10034

Birmingham, Alabama, United States

Site US10024

Homewood, Alabama, United States

Site US10007

Tucson, Arizona, United States

Site US10055

Tucson, Arizona, United States

Site US10004

Los Angeles, California, United States

Site US10026

Sacramento, California, United States

Site US10010

San Diego, California, United States

Site US10051

Aurora, Colorado, United States

Site US10029

Denver, Colorado, United States

Site US10054

Denver, Colorado, United States

Site US10072

Bradenton, Florida, United States

Site US10057

Lakeland, Florida, United States

Site US10038

Chicago, Illinois, United States

Site US10062

Chicago, Illinois, United States

Site US10074

Chicago, Illinois, United States

Site US10018

Glenview, Illinois, United States

Site US10071

Lake Barrington, Illinois, United States

Site US10046

Carmel, Indiana, United States

Site US10009

Jeffersonville, Indiana, United States

Site US10037

New Orleans, Louisiana, United States

Site US10006

Shreveport, Louisiana, United States

Site US10001

Towson, Maryland, United States

Site US10032

Boston, Massachusetts, United States

Site US10008

Troy, Michigan, United States

Site US10069

Lincoln, Nebraska, United States

Site US10044

Omaha, Nebraska, United States

Site US10067

Omaha, Nebraska, United States

Site US10061

Lebanon, New Hampshire, United States

Site US10049

Morristown, New Jersey, United States

Site US10043

Voorhees Township, New Jersey, United States

Site US10068

Brooklyn, New York, United States

Site US10050

Cheektowaga, New York, United States

Site US10030

Garden City, New York, United States

Site US10028

Poughkeepsie, New York, United States

Site US10021

Syracuse, New York, United States

Site US10022

Syracuse, New York, United States

Site US10047

Gastonia, North Carolina, United States

Site US10045

Cleveland, Ohio, United States

Site US10015

Middleburg Heights, Ohio, United States

Site US10053

Oklahoma City, Oklahoma, United States

Site US10063

Bala-Cynwyd, Pennsylvania, United States

Site US10052

Lancaster, Pennsylvania, United States

Site US10014

Warwick, Rhode Island, United States

Site US10019

Myrtle Beach, South Carolina, United States

Site US10011

Nashville, Tennessee, United States

Site US10056

Dallas, Texas, United States

Site US10036

Houston, Texas, United States

Site US10035

San Antonio, Texas, United States

Site US10058

Richmond, Virginia, United States

Site US10017

Milwaukee, Wisconsin, United States

Site CA15005

Abbotsford, British Columbia, Canada

Site CA15004

Halifax, Nova Scotia, Canada

Site CA15001

Toronto, Ontario, Canada

Site CA15003

Toronto, Ontario, Canada

Countries

United States; Canada

References

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 Jul 31. doi: 10.1111/bju.16861. Online ahead of print.

Reference Type: DERIVED

PMID: 40742002 (View on PubMed)

Ross 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.

Reference Type: DERIVED

PMID: 38635932 (View on PubMed)

Shore 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.

Reference Type: DERIVED

PMID: 35708696 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.clinicaltrials.astellas.com/study/?pid=9785-MA-1010

Link to results and other applicable study documents on the Astellas Clinical Trials website

https://www.trialsummaries.com/Study/StudyDetails?id=14506&tenant=MT_AST_9011

Link to plain language summary of the study on the Trial Results Summaries website

Other Identifiers

9785-MA-1010

Identifier Type: -

Identifier Source: org_study_id