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

Prostate Cancer Clinical Trial

— ENACT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02799745
• Other study ID #: 9785-MA-1010
• Status: Completed
• Phase: Phase 2
• Start date: June 9, 2016
• Est. completion date: August 28, 2020

Study information

• Verified date: October 2021
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: August 28, 2020
• Est. primary completion date: August 28, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Enzalutamide
Oral

Other:
• Active Surveillance

Locations

Country	Name	City	State
Canada	Site CA15005	Abbotsford	British Columbia
Canada	Site CA15004	Halifax	Nova Scotia
Canada	Site CA15001	Toronto	Ontario
Canada	Site CA15003	Toronto	Ontario
United States	Site US10051	Aurora	Colorado
United States	Site US10063	Bala-Cynwyd	Pennsylvania
United States	Site US10034	Birmingham	Alabama
United States	Site US10032	Boston	Massachusetts
United States	Site US10072	Bradenton	Florida
United States	Site US10068	Brooklyn	New York
United States	Site US10046	Carmel	Indiana
United States	Site US10050	Cheektowaga	New York
United States	Site US10038	Chicago	Illinois
United States	Site US10062	Chicago	Illinois
United States	Site US10074	Chicago	Illinois
United States	Site US10045	Cleveland	Ohio
United States	Site US10056	Dallas	Texas
United States	Site US10029	Denver	Colorado
United States	Site US10054	Denver	Colorado
United States	Site US10030	Garden City	New York
United States	Site US10047	Gastonia	North Carolina
United States	Site US10018	Glenview	Illinois
United States	Site US10024	Homewood	Alabama
United States	Site US10036	Houston	Texas
United States	Site US10009	Jeffersonville	Indiana
United States	Site US10071	Lake Barrington	Illinois
United States	Site US10057	Lakeland	Florida
United States	Site US10052	Lancaster	Pennsylvania
United States	Site US10061	Lebanon	New Hampshire
United States	Site US10069	Lincoln	Nebraska
United States	Site US10004	Los Angeles	California
United States	Site US10015	Middleburg Heights	Ohio
United States	Site US10017	Milwaukee	Wisconsin
United States	Site US10049	Morristown	New Jersey
United States	Site US10019	Myrtle Beach	South Carolina
United States	Site US10011	Nashville	Tennessee
United States	Site US10037	New Orleans	Louisiana
United States	Site US10053	Oklahoma City	Oklahoma
United States	Site US10044	Omaha	Nebraska
United States	Site US10067	Omaha	Nebraska
United States	Site US10028	Poughkeepsie	New York
United States	Site US10058	Richmond	Virginia
United States	Site US10026	Sacramento	California
United States	Site US10035	San Antonio	Texas
United States	Site US10010	San Diego	California
United States	Site US10006	Shreveport	Louisiana
United States	Site US10021	Syracuse	New York
United States	Site US10022	Syracuse	New York
United States	Site US10001	Towson	Maryland
United States	Site US10008	Troy	Michigan
United States	Site US10007	Tucson	Arizona
United States	Site US10055	Tucson	Arizona
United States	Site US10043	Voorhees	New Jersey
United States	Site US10014	Warwick	Rhode Island

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Medivation LLC, a wholly owned subsidiary of Pfizer Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of Participants With Adverse Events (AEs)	An AE: any untoward medical occurrence in a participant administered study drug or who underwent study procedures and did not necessarily had a causal relationship with treatment. An abnormality identified during a medical test: an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption, or discontinuation of study medication, or was clinically significant in the opinion of investigator. An AE: serious if it resulted in any of the following outcomes: Death, was life-threatening, Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, Congenital anomaly, or birth defect, Inpatient hospitalization or prolongation of hospitalization, Other medically important event. Drug-related AEs: assessed by investigator as AEs whose relationship to study drugs could not be ruled out.	From date of first dose of enzalutamide or randomization until end of study (up to study completion date, 28 Aug 2020; approximately 50 months)
Secondary	Percentage of Participants Reported Negative Biopsies for Cancer	Percentage of Participants who reported negative biopsies for cancer were reported.	At the end of months 12 and 24
Secondary	Change From Baseline in Percent of Cancer Positive Cores at Month 12 and 24	Percent positive cores were calculated using the number of systemically sampled prostate regions and any targeted regions with at least 1 positive core divided by the total number of systematically sampled regions and targeted regions. This implied that despite the number of samples within a given systematic or targeted region, any positive core indicated that region as positive.	Baseline, months 12 and 24
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Time to PSA progression was defined as time in months from the date of randomization or first dose enzalutamide untill date of PSA progression (secondary rise in serum PSA >=25% above baseline or >=25% above nadir or absolute increase >= 2 nanogram per mililiter [ng/mL]). Participants with no PSA progression at the time of trial completion, discontinuation or death were censored at the last assessment date. Additionally, 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. Medians and 95% CIs were calculated with the KM method.	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")
Secondary	Percentage of Participants With Secondary Rise in Serum PSA	Percentage of participants with secondary rise in serum PSA > 25% baseline or > 25% above nadir or absolute increase >2 ng/mL were reported in this measure.	At the end of months 12, 24 and at the end of study (up to study completion date, 28 Aug 2020, approximately 50 months)
Secondary	Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire Composite Scores to Months 3, 6, 12, 18 and 24	The BFI is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A composite fatigue score was obtained by averaging all the items on the BFI, ranged between 0 to 10, with a higher BFI fatigue score indicating worse outcome. The composite BFI score was calculated only if at least 5 of the 9 items were answered.	Baseline, months 3, 6, 12, 18 and 24
Secondary	Change From Baseline in 12-Item Short Form Survey (SF-12) Questionnaire Composite Score to Months 6, 12, 18, 24 - Mental Component Summary	SF-12 is a questionnaire that measures overall health related quality of life using 12 questions. The questions are then scored and weighted into 2 subscales, physical health and mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life). Scores are transformed and ranges between 0 to 100; higher score indicates improvement.	Baseline, months 6, 12, 18 and 24
Secondary	Change From Baseline in SF-12 Questionnaire Composite Score to Months 6, 12, 18, 24 - Physical Component Summary	SF-12 is a questionnaire that measures overall health related quality of life using 12 questions. The questions are then scored and weighted into 2 subscales, physical health and mental health. Each yields scores from 0 (representing the worst possible debilitation) to 100 (representing no reduction in quality of life). Scores are transformed and ranges between 0 to 100; higher score indicates improvement.	Baseline, months 6, 12, 18 and 24
Secondary	Change From Baseline in The Expanded Prostate Cancer Index Composite (EPIC) Hormonal Assessment Scores at Months 6, 12, 18 and 24	The EPIC Hormonal Assessment was a questionnaire used to measure quality of life (QoL) issues in participants with prostate cancer. There were a total of 6 questions related to hormonal function such as hot flashes, breast tenderness, depression, lack of energy, weight fluctuation. The answers ranged from "more than once a day" to "rarely or never" (ranged from 1 to 5, corresponding standardized scores were 100, 75, 50, 25, 0), "no problem" to "big problem" (ranged from 0 to 4, corresponding standardized scores were 100, 75, 50, 25, 0). Score from each answer was converted into standardized score at each visit. Total score was calculated by taking average of standardized scores. Total score was measured on a scale ranged from 0 (worst) to 100 (best) scale with higher scores representing better hormonal function.	Baseline, months 6, 12, 18 and 24
Secondary	Change From Baseline in EPIC Sexual Assessment Scores at Months 6, 12, 18 and 24	EPIC Sexual Assessment: a questionnaire to measure QoL issues in participants with prostate cancer, included a total of 9 questions on sexual function as level of sexual desire, ability to have an erection, ability to reach orgasm, quality and frequency of erections, frequency of sexual intercourse. Answers ranged from "very poor" to "very good,"(ranged from 1 - 5, corresponding standardized scores:0, 25, 50, 75, 100), "none" to "enough"(ranged from 1 - 4, corresponding standardized scores:0, 33, 67, 100), "no problem" to "big problem"(ranged from 0 - 4, corresponding standardized scores:100, 75, 50, 25, 0), and "never" to "daily"(ranged from 1 - 5, corresponding standardized scores:100, 75, 50, 25, 0). Scores from each answer was converted into standardized score at each visit. Total score = calculated by taking average of standardized scores. Total score was measured on a scale ranged from 0 (worst) to 100 (best), higher scores = better sexual function and satisfaction.	Baseline, months 6, 12, 18 and 24
Secondary	Change From Baseline in EPIC Urinary Assessment Scores at Month 6, 12, 18 and 24	EPIC urinary assessment: a questionnaire to measure QoL issues in participants with prostate cancer, included a total of 7 questions on urinary function as leaking urine, blood in urine, pain/burning on urination, urinary control and frequency. Answers ranged from "more than once a day" to "rarely or never"(scores from 1 - 5,corresponding standardized scores[CSS]:0, 25, 50, 75, 100), "no urinary control" to "full urinary control"(scores from 1 - 4,CSS:0, 33, 67, 100), "none" to "3 or more pads per day"(scores from 0 - 3, CSS:100, 67, 33, 0), "no problem" to "big problem"(scores from 0 - 4, CSS:100, 75, 50, 25, 0), and "no problem" to "big problem"(scores from 1 - 5, corresponding standardized score:100, 75, 50, 25, 0). Score from each answer was converted into a corresponding standardized score at each visit. Total score was calculated by taking average of standardized scores. Total score ranged from 0(worst) to 100(best), higher scores = better urinary function.	Baseline, months 6, 12, 18 and 24
Secondary	Change From Baseline in Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Scores at Months 6, 12, 18 and 24	The MAX-PC was a questionnaire used to assess participants' feelings about prostate cancer and PSA tests. There were a total of 18 questions related to understanding how participants cope with aspects of their treatment and medical tests frequently involved in their care; questions such as strong feelings about prostate cancer, scared of PSA tests, trouble sleeping due to thoughts of prostate cancer, unable to plan for the future due to prostate cancer, fear of cancer getting worse. The answers range from "not at all" to "often" and "strongly disagree" to "strongly agree. Total score ranged from 0-54, an increase in the score indicates a worsened anxiety level.	Baseline, months 6, 12, 18 and 24

External Links

•   Link to plain language summary of the study on the Trial Results Summaries website
•   Link to results and other applicable study documents on the Astellas Clinical Trials website