Testing the Effects of Low Dose Apalutamide on Prostate-Specific Antigen (PSA) Levels in Men Scheduled for Removal of the Prostate Gland

Clinical Study of Bioactivity of Low Dose Apalutamide in Prostate Cancer Patients Scheduled for Prostatectomy

Apalutamide is an anti-androgen that blocks the effect of testosterone on prostate cancer growth. This phase IIa trial is designed to determine whether very low doses of apalutamide, given for 3 to 4 weeks before prostate surgery to men with prostate cancer confined to the prostate gland, reduces plasma levels of PSA (a biomarker of apalutamide's ability to block testosterone). If low dose apalutamide lowers PSA levels in this setting, further study of this agent in men with localized prostate cancer who wish to delay definitive therapy with surgery or radiation may be warranted.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Adenocarcinoma; Localized Prostate Carcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8
• Intervention / Treatment: Other: Quality-of-Life Assessment; Procedure: Biospecimen Collection; Drug: Apalutamide

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the effects of low dose apalutamide on circulating levels of prostate specific antigen (PSA).

SECONDARY OBJECTIVES:

I. To determine the effect of low dose apalutamide on:

Ia. Reversibility of testosterone levels 7-14 days post intervention; Ib. Post-intervention plasma trough apalutamide concentration; Ic. Health-related quality of life.

EXPLORATORY OBJECTIVE:

I. To determine the effects of apalutamide on intra-prostatic immune cell infiltration and Gleason score and the effects of tobacco/alcohol use on the study endpoints.

OUTLINE:

Patients receive apalutamide orally (PO) on study. Patients also undergo collection of blood samples throughout the study.

After completion of the trial intervention, patients are followed up at 7-10 days and at 60 days.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center - Prevention Research Clinic
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20037
      • George Washington University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Bethesda, Maryland, United States, 20892
      • NCI - Center for Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed organ-confined adenocarcinoma of the prostate (PCa) suitable for prostatectomy
• Gleason score =< (4+4), however no Gleason pattern 5
• Current serum PSA =< 20 ng/ml
• Age > 18 years
• Karnofsky >= 70%
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (note: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject may be eligible)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 2.5 x institutional ULN
• Creatinine < 2 x institutional ULN
• Thyroid stimulating hormone (TSH) within the institutional normal range
• Willing to use adequate contraception (barrier method; abstinence; subject has had a vasectomy; or partner is using effective birth control or is postmenopausal) for the duration of study participation
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior or ongoing hormonal treatment for prostate cancer including, but not limited to orchiectomy, antiandrogens, abiraterone, ketoconazole, or estrogens, or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists. Men on stable doses of 5-alpha reductase inhibitors (e.g., finasteride, dutasteride) are eligible as long as there is no planned dose change while on study
• Patients who have prostate cancer with distant metastases
• Presence of neuroendocrine differentiation in the prostate biopsies
• Serum testosterone (blood collected between 7-10 AM for men < 45 years of age and prior to 2 PM for men >= 45 years of age) < 200 ng/dL
• Have a history of prior malignancies other than prostate cancer within the past 2 years, excluding non-melanoma skin cancer
• Severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration
• History of seizure or known condition that may pre-dispose to seizure (including but not limited to prior stroke, transient ischemic attack, loss of consciousness within 1 year prior to registration, brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
• Use of drugs known to lower the seizure threshold, including: atypical antipsychotics (e.g. clozapine, olanzapine, risperidone, ziprasidone), bupropion, lithium, meperidine, pethidine, phenothiazine antipsychotics (e.g. chlorpromazine, mesoridazine, thioridazine), and tricyclic antidepressants (e.g. amitriptyline, desipramine, doxepin, imipramine, maprotiline, mirtazapine)
• Concurrent use of drugs in category X drug interactions with apalutamide
• Participants may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical composition of apalutamide
• Uncontrolled intermittent illnesses or medical conditions which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. Such illnesses/conditions may include, but are not limited to, hypertension, ongoing or active infection, or psychiatric illness/social situations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (apalutamide); Patients receive apalutamide PO on study. Patients also undergo collection of blood samples throughout the study.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Drug: Apalutamide; Given PO; Other Names: ARN-509; JNJ-56021927; ARN 509; ARN509; Erleada; JNJ 56021927

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Prostate Specific Antigen (PSA) Levels	The proportion of participants with >= 25% decline in PSA levels (from baseline to end-of-intervention) will be reported along with the 97.5% credible interval for the response rate based on the posterior distribution of the response rate derived from a non-informative prior for the response rate, which is consistent with the Bayesian approach.	Baseline to end-of-intervention (mean 4.8 weeks; up to 9 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reversibility of Testosterone Levels	Mean change in testosterone from end-of-intervention to post-operation	End-of-intervention to post-operation (mean 2.7 days; up to 7 days)
Post-intervention Plasma Trough Apalutamide Concentrations	Correlation between plasma apalutamide and percent change of PSA levels	End-of-intervention (mean 4.8 weeks; up to 9 weeks)
Health-related Quality of Life (HRQOL)	Expanded Prostate Cancer Index Composite for Clinical Practice [EPIC-CP]. Higher scores indicate worse outcome (more symptoms). The minimum and maximum values for the total score are 0 to 60. A negative change indicates that the score decreased and therefore is a better outcome (reduced symptoms).	Baseline to end of intervention (mean 4.8 weeks; up to 9 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gleason Score of Pre- and Post-intervention Tumor(s) With Matched Location	Changes (from most recent biopsy to prostatectomy) in the Gleason score of pre- and post-intervention tumor(s) with matched location will be assessed for each dose group. Linear mixed effects model with a random intercept accounting for within-subject dependence will be performed to compare the change in Gleason score of pre- and post-intervention tumor(s) with matched location since a participant can have more than one tumor. A 95% Cl will be reported for each of the two dose groups.	Up to 7-14 days after prostate surgery
Intra-prostatic Immune Cell Infiltration	CD8+, CD4+, and CD56+ positive cells in the prostate tissues will be assessed by immunohistochemistry. Changes (from most recent biopsy to prostatectomy) in these immune cells will be assessed for each dose group. Changes in immune cel infiltration will also be assessed in a subgroup of participants where materials are available from pre- and post-intervention tumors) with matched location. Changes (from most recent biopsy to prostatectomy) in these immune cells will be assessed for each dose group by paired t test. A 95% Cl will be reported for each of the two dose groups.	Up to 7-14 days after prostate surgery
Effects of Tobacco/Alcohol Use	Will be assessed by examining the associations between tobacco and alcohol consumption and the effects of apalutamide on the study endpoints.	Baseline, every 7-10 during study, within 3 days prior to surgery, and 7-14 days after surgery

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Juan Chipollini, University of Arizona Cancer Center - Prevention Research Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2021
• Primary Completion (Actual): November 6, 2024
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: August 27, 2020
• First Submitted That Met QC Criteria: August 27, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; apalutamide
• Other Study ID Numbers: NCI-2020-06322 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 2102475889 (Other Identifier: University of Arizona Cancer Center - Prevention Research Clinic); UAZ20-01-01 (Other Identifier: DCP); P30CA023074 (U.S. NIH Grant/Contract); UG1CA242596 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No