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

Prostate Adenocarcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04530552
• Other study ID #: NCI-2020-06322
• Secondary ID: NCI-2020-0632221
• Status: Recruiting
• Phase: Phase 2
• Start date: July 23, 2021
• Est. completion date: January 31, 2027

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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, 60 days, and 3 months post-prostatectomy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 31, 2027
• Est. primary completion date: January 31, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Adenocarcinoma
• Prostatic Neoplasms
• Stage I Prostate Cancer AJCC v8
• Stage II Prostate Cancer AJCC v8

Intervention

Drug:
• Apalutamide
Given PO

Procedure:
• Biospecimen Collection
Undergo collection of blood samples

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	NCI - Center for Cancer Research	Bethesda	Maryland
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	University of Arizona Cancer Center - Prevention Research Clinic	Tucson	Arizona
United States	George Washington University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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 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.	Up to 7-14 days after prostate surgery
Other	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 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.	Up to 7-14 days after prostate surgery
Other	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
Primary	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 up to end of treatment
Secondary	Reversibility of testosterone levels	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.	Baseline, and at 7-14 days post-intervention (post-operative)
Secondary	Post-intervention plasma trough apalutamide concentrations	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.	Up to 7-14 days after prostate surgery
Secondary	Health-related quality of life (HRQOL)	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.	Baseline, until end of intervention