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

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ClinicalTrials.gov Identifier: NCT04530552
Recruitment Status : Recruiting
First Posted : August 28, 2020
Last Update Posted : June 18, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase IIa trial investigates how well apalutamide before surgery works in treating patients with prostate cancer that is confined to the prostate gland. Testosterone can cause the growth of prostate cancer cells. 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 that is confined to the prostate gland.

Condition or disease Intervention/treatment Phase
Prostate Adenocarcinoma Drug: Apalutamide 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. Intra-prostatic immune cell infiltration. Id. Health-related quality of life. Ie. Gleason score of pre- and post-intervention tumor(s) with matched location.

OUTLINE:

The first 40 patients taking part in this trial receive apalutamide orally (PO) three times a week (TIW) for 4-8 weeks prior to before prostate surgery in the absence of disease progression or unacceptable toxicity. Based on PSA levels of the first 40 patients, the next group of 40 patients receive apalutamide either once a week (QW) or once daily (QD) for 4-8 weeks prior to before prostate surgery in the absence of disease progression or unacceptable toxicity. Patients may receive apalutamide for up to 12 weeks before prostate surgery (in the event surgery is delayed).

After completion of study treatment, patients are followed up at 7-14 days after prostate surgery.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : April 30, 2023
Estimated Study Completion Date : September 30, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Apalutamide

Arm Intervention/treatment
Experimental: Treatment (apalutamide)
The first 40 patients taking part in this trial receive apalutamide PO TIW for 4-8 weeks prior to before prostate surgery in the absence of disease progression or unacceptable toxicity. Based on PSA levels of the first 40 patients, the next group of 40 patients receive apalutamide either QW or QD for 4-8 weeks prior to before prostate surgery in the absence of disease progression or unacceptable toxicity. Patients may receive apalutamide for up to 12 weeks before prostate surgery (in the event surgery is delayed).
Drug: Apalutamide
Given PO
Other Names:
  • ARN 509
  • ARN-509
  • ARN509
  • Erleada
  • JNJ 56021927
  • JNJ-56021927

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




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 determined for each dose cohort. Paired t test will be performed on the changes in PSA to evaluate the effects of low dose apalutamide for each dose group. The dose level of the second dose group can be higher than the first dose group (i.e. does escalation). Therefore, we conservatively use Bonferroni correction to control for multiple comparisons for the primary endpoint analysis since a gate-keeping procedure based on the test result of the first dose group will be inappropriate when does escalation occurs.


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. 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.

  4. 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.

  5. 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.

  6. Incidence of adverse events [ Time Frame: From the time of first dose of apalutamide, up to 7-14 days after prostate surgery ]
    Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals.



Information from the National Library of Medicine

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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)
  • Current serum PSA < 10 ng/ml OR PSA >= 10 ng/ml with PSA density < 0.3 ng/ml^2.
  • 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 and for 3 months following the last dose of study drug; must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug
  • 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) < 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04530552


Locations
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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 Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Mike M. Nguyen    323-865-3041    Mike.Nguyen@med.usc.edu   
Principal Investigator: Mike M. Nguyen         
University of California San Diego 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, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center Not yet 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 Not yet 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
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Principal Investigator: John K Parsons University of Arizona Cancer Center - Prevention Research Clinic
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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) )
UAZ20-01-01 ( 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    Key Record Dates
Last Update Posted: June 18, 2021
Last Verified: June 2021
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms