Clinical trial NCT02799745: A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance
Official title: A Randomized Study of Enzalutamide in Patients With Localized Prostate Cancer Undergoing Active Surveillance (ENACT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: Therapeutic Cancer Progression
Pathological Cancer Progression
Enzalutamide
Prostate Cancer
Active surveillance
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
First posted: 2016-06-15
Enrollment: 227
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to Prostate Cancer Progression
timeFrame: 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:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020; approximately 50 months)
measure: Percentage of Participants Reported Negative Biopsies for Cancer
timeFrame: At the end of months 12 and 24
measure: Change From Baseline in Percent of Cancer Positive Cores at Month 12 and 24
timeFrame: Baseline, months 12 and 24
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: 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")
measure: Percentage of Participants With Secondary Rise in Serum PSA
timeFrame: At the end of months 12, 24 and at the end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
measure: Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24
timeFrame: Baseline, months 3, 6, 12, 18 and 24
measure: Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary
timeFrame: Baseline, months 6, 12, 18 and 24
measure: Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary
timeFrame: Baseline, months 6, 12, 18 and 24
measure: Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24
timeFrame: Baseline, months 6, 12, 18 and 24
measure: Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24
timeFrame: Baseline, months 6, 12, 18 and 24
measure: Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24
timeFrame: Baseline, months 6, 12, 18 and 24
measure: Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24
timeFrame: Baseline, months 6, 12, 18 and 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site US10034
state: Alabama
city: Homewood
country: United States
facility: Site US10024
state: Alabama
city: Tucson
country: United States
facility: Site US10007
state: Arizona
city: Tucson
country: United States
facility: Site US10055
state: Arizona
city: Los Angeles
country: United States
facility: Site US10004
state: California
city: Sacramento
country: United States
facility: Site US10026
state: California
city: San Diego
country: United States
facility: Site US10010
state: California
city: Aurora
country: United States
facility: Site US10051
state: Colorado
city: Denver
country: United States
facility: Site US10029
state: Colorado
city: Denver
country: United States
facility: Site US10054
state: Colorado
city: Bradenton
country: United States
facility: Site US10072
state: Florida
city: Lakeland
country: United States
facility: Site US10057
state: Florida
city: Chicago
country: United States
facility: Site US10038
state: Illinois
city: Chicago
country: United States
facility: Site US10062
state: Illinois
city: Chicago
country: United States
facility: Site US10074
state: Illinois
city: Glenview
country: United States
facility: Site US10018
state: Illinois
city: Lake Barrington
country: United States
facility: Site US10071
state: Illinois
city: Carmel
country: United States
facility: Site US10046
state: Indiana
city: Jeffersonville
country: United States
facility: Site US10009
state: Indiana
city: New Orleans
country: United States
facility: Site US10037
state: Louisiana
city: Shreveport
country: United States
facility: Site US10006
state: Louisiana
city: Towson
country: United States
facility: Site US10001
state: Maryland
city: Boston
country: United States
facility: Site US10032
state: Massachusetts
city: Troy
country: United States
facility: Site US10008
state: Michigan
city: Lincoln
country: United States
facility: Site US10069
state: Nebraska
city: Omaha
country: United States
facility: Site US10044
state: Nebraska
city: Omaha
country: United States
facility: Site US10067
state: Nebraska
city: Lebanon
country: United States
facility: Site US10061
state: New Hampshire
city: Morristown
country: United States
facility: Site US10049
state: New Jersey
city: Voorhees
country: United States
facility: Site US10043
state: New Jersey
city: Brooklyn
country: United States
facility: Site US10068
state: New York
city: Cheektowaga
country: United States
facility: Site US10050
state: New York
city: Garden City
country: United States
facility: Site US10030
state: New York
city: Poughkeepsie
country: United States
facility: Site US10028
state: New York
city: Syracuse
country: United States
facility: Site US10021
state: New York
city: Syracuse
country: United States
facility: Site US10022
state: New York
city: Gastonia
country: United States
facility: Site US10047
state: North Carolina
city: Cleveland
country: United States
facility: Site US10045
state: Ohio
city: Middleburg Heights
country: United States
facility: Site US10015
state: Ohio
city: Oklahoma City
country: United States
facility: Site US10053
state: Oklahoma
city: Bala-Cynwyd
country: United States
facility: Site US10063
state: Pennsylvania
city: Lancaster
country: United States
facility: Site US10052
state: Pennsylvania
city: Warwick
country: United States
facility: Site US10014
state: Rhode Island
city: Myrtle Beach
country: United States
facility: Site US10019
state: South Carolina
city: Nashville
country: United States
facility: Site US10011
state: Tennessee
city: Dallas
country: United States
facility: Site US10056
state: Texas
city: Houston
country: United States
facility: Site US10036
state: Texas
city: San Antonio
country: United States
facility: Site US10035
state: Texas
city: Richmond
country: United States
facility: Site US10058
state: Virginia
city: Milwaukee
country: United States
facility: Site US10017
state: Wisconsin
city: Abbotsford
country: Canada
facility: Site CA15005
state: British Columbia
city: Halifax
country: Canada
facility: Site CA15004
state: Nova Scotia
city: Toronto
country: Canada
facility: Site CA15001
state: Ontario
city: Toronto
country: Canada
facility: Site CA15003
state: Ontario
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.