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

• ClinicalTrials.gov Identifier: NCT04530552
• Recruitment Status: Recruiting
• First Posted: August 28, 2020
• Last Update Posted: April 3, 2023
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

This phase IIa trial investigates the biomarker (plasma levels of PSA) of low-dose apalutamide in patients with prostate cancer confined in the prostate gland before surgery. Testosterone can cause the growth of prostate cancer cells, and Apalutamide blocks the use of testosterone by the tumor cells. Giving low-dose apalutamide before prostate surgery may lead to lowered PSA levels in men with prostate cancer confined to the prostate gland.

Condition or disease	Intervention/treatment	Phase
Localized Prostate Carcinoma; Prostate Adenocarcinoma; Stage I Prostate Cancer AJCC v8; Stage II Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8	Drug: Apalutamide; Procedure: Biospecimen Collection; Other: Quality-of-Life Assessment	Phase 2

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 as exploratory endpoints.

OUTLINE:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Clinical Study of Bioactivity of Low Dose Apalutamide in Prostate Cancer Patients Scheduled for Prostatectomy
• Actual Study Start Date: June 1, 2021
• Estimated Primary Completion Date: August 31, 2024
• Estimated Study Completion Date: August 31, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change in prostate specific antigen (PSA) levels [ Time Frame: Baseline up to end of treatment ]
   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.

Secondary Outcome Measures :

1. Reversibility of testosterone levels [ Time Frame: Baseline, and at 7-14 days post-intervention (post-operative) ]
   The post-operative testosterone levels will be compared with the levels at baseline and end-of-intervention within each dose cohort. Paired t test will be performed on the changes in testosterone to evaluate the effects of low dose apalutamide for each dose group. A 95% CI will be reported for each of the two dose groups.
2. Post-intervention plasma trough apalutamide concentrations [ Time Frame: Up to 7-14 days after prostate surgery ]
   Post-intervention plasma trough apalutamide concentrations will be quantified by a sensitive and specific liquid chromatography mass spectrometry assay. The correlation between plasma trough apalutamide and the change of PSA levels will be assessed. Pearson correlation coefficient will be derived to evaluate the correlation between the plasma trough apalutamide levels and the change of PSA levels. A 95% CI will be reported for each of the two dose groups.
3. Health-related quality of life (HRQOL) [ Time Frame: Baseline, until end of intervention ]
   HRQOL will be assessed by a validated questionnaire (Expanded Prostate Cancer Index Composite for Clinical Practice [EPIC-CP]) to allow for efficient and accurate measurement of urinary incontinence, urinary irritation, bowel, sexual, and hormonal HRQOL in prostate cancer patients. Changes (from baseline to end-of-intervention) in the overall score and subscore for each measure will be assessed for each dose group. Changes in EPIC-CP (from baseline to end-of-intervention) in the overall score and sub-score for each measure will be derived and paired t test will be performed to evaluate the change for each dose group. A 95% CI will be reported for each of the two dose groups.

Other Outcome Measures:

1. Gleason score of pre- and post-intervention tumor(s) with matched location [ Time Frame: Up to 7-14 days after prostate surgery ]
   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 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% CI will be reported for each of the two dose groups.
2. Intra-prostatic immune cell infiltration [ Time Frame: Up to 7-14 days after prostate surgery ]
   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 cell infiltration will also be assessed in a subgroup of participants where materials are available from pre- and post-intervention tumor(s) 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% CI will be reported for each of the two dose groups.
3. Effects of tobacco/alcohol use [ Time Frame: Baseline, every 7-10 during study, within 3 days prior to surgery, and 7-14 days after surgery ]
   Will be assessed by examining the associations between tobacco and alcohol consumption and the effects of apalutamide on the study endpoints.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

University of Arizona Cancer Center - Prevention Research Clinic; Recruiting

Tucson, Arizona, United States, 85719

Contact: Hsiao-Hui (Sherry) Chow 520-626-3358 schow@azcc.arizona.edu

Principal Investigator: Hsiao-Hui (Sherry) Chow

United States, California

USC / Norris Comprehensive Cancer Center; Recruiting

Los Angeles, California, United States, 90033

Contact: Mike M. Nguyen 323-865-3041 Mike.Nguyen@med.usc.edu

Principal Investigator: Mike M. Nguyen

UC San Diego Medical Center - Hillcrest; Not yet recruiting

San Diego, California, United States, 92103

Contact: John K. Parsons 858-822-7874 K0parsons@mail.ucsd.edu

Principal Investigator: John K. Parsons

United States, District of Columbia

George Washington University Medical Center; Recruiting

Washington, District of Columbia, United States, 20037

Contact: Michael J. Whalen 202-741-3121 mwhalen@mfa.gwu.edu

Principal Investigator: Michael J. Whalen

United States, Maryland

Johns Hopkins University/Sidney Kimmel Cancer Center; Recruiting

Baltimore, Maryland, United States, 21287

Contact: Christian P. Pavlovich 410-550-3338 cpavlov2@jhmi.edu

Principal Investigator: Christian P. Pavlovich

NCI - Center for Cancer Research; Recruiting

Bethesda, Maryland, United States, 20892

Contact: Peter A. Pinto 301-496-6353 pintop@mail.nih.gov

Principal Investigator: Peter A. Pinto

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Juan Chipollini; University of Arizona Cancer Center - Prevention Research Clinic

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT04530552
• Other Study ID Numbers: NCI-2020-06322; 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 )
• First Posted: August 28, 2020
• Last Update Posted: April 3, 2023
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• URL: https://grants.nih.gov/policy/sharing.htm

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases