Clinical trial NCT04530552: Testing the Effects of Low Dose Apalutamide on Prostate-Specific Antigen (PSA) Levels in Men Scheduled for Removal of the Prostate Gland
Official title: Clinical Study of Bioactivity of Low Dose Apalutamide in Prostate Cancer Patients Scheduled for Prostatectomy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Localized Prostate Carcinoma
Prostate Adenocarcinoma
Stage I Prostate Cancer AJCC v8
Stage II Prostate Cancer AJCC v8
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2020-08-28
Enrollment: 34
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief 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.

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, 60 days, and 3 months post-prostatectomy.

Eligibility 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

Primary outcomes:
measure: Change in prostate specific antigen (PSA) levels
timeFrame: Baseline up to end of treatment
Secondary outcomes:
measure: Reversibility of testosterone levels
timeFrame: Baseline, and at 7-14 days post-intervention (post-operative)
measure: Post-intervention plasma trough apalutamide concentrations
timeFrame: Up to 7-14 days after prostate surgery
measure: Health-related quality of life (HRQOL)
timeFrame: Baseline, until end of intervention
Other outcomes:
measure: Gleason score of pre- and post-intervention tumor(s) with matched location
timeFrame: Up to 7-14 days after prostate surgery
measure: Intra-prostatic immune cell infiltration
timeFrame: Up to 7-14 days after prostate surgery
measure: Effects of tobacco/alcohol use
timeFrame: Baseline, every 7-10 during study, within 3 days prior to surgery, and 7-14 days after surgery
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - Prevention Research Clinic
state: Arizona
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: NCI - Center for Cancer Research
state: Maryland
Study officials:
affiliation: University of Arizona Cancer Center - Prevention Research Clinic
name: Juan Chipollini
role: PRINCIPAL_INVESTIGATOR
References: