Apalutamide in Treating Patients With Prostate Cancer Who Are in Active Surveillance

Study Overview
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Brief Summary
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This phase II trial studies how well apalutamide works in treating patients with prostate cancer who are in active surveillance. Testosterone can cause the growth of prostate cancer cells. Hormone therapy using androgen receptor antagonist apalutamide may fight prostate cancer by blocking the use of testosterone by the tumor cells.

Detailed Description
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OUTLINE: Patients receive apalutamide orally (PO) once daily (QD) for 90 days in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients are followed up at 180, 365, 545, and 730 days; and at years 3, 4 and 5 by medical record review.

Official Title
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A Phase 2 Study of Apalutamide in Active Surveillance Patients

Conditions
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Prostate Adenocarcinoma

Intervention / Treatment
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* Drug: Apalutamide
* Other: Laboratory Biomarker Analysis
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have signed an informed consent document Be willing/able to adhere to the prohibitions and restrictions specified in this protocol Written authorization for use and release of health and research study information has been obtained Life expectancy >= 10 years (as determined by the treating physician) Eastern Cooperative Oncology Group (ECOG) performance status =< 1 Histologically confirmed adenocarcinoma of the prostate as documented by a minimum 12 core prostate biopsy completed within 1-year of enrollment (note: most recent prostate biopsy must have demonstrated prostatic adenocarcinoma) Favorable risk prostate cancer as defined by: Very low-risk: Clinical stage T1c disease PSA density (PSAD) < 0.15 ng/mL Gleason score 6 =< 2 core biopsies with =< 50% involvement of any biopsy core with cancer, or unilateral disease =< 2 core biopsies with any percentage involvement OR Low risk: Clinical stage =< T2a PSA < 15 ng/mL Gleason score 6 OR Low-intermediate risk: Clinical stage T1c PSA < 15 ng/ml Gleason 3+4 present in =< 50% of one core/site as detected by systematic biopsy or MRI/transrectal ultrasound (TRUS) fusion guided biopsy Gleason 6 disease in all other cores / sites Willing and qualified for active surveillance at Johns Hopkins or the University of Washington Serum testosterone >= 150 ng/dL Able to swallow the study drugs whole as a tablet Hemoglobin >= 9.0 g/dL, (at screening), independent of transfusion and/or growth factors within 3 months prior to registration Platelet count >= 100,000 x 10^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to registration Serum albumin >= 3.0 g/dL (at screening) Glomerular filtration rate (GFR) >= 45 mL/min (at screening) Serum potassium >= 3.5 mmol/L (at screening) Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (at screening) (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) or alanine aminotransferase (ALT) < 2.5 × ULN (at screening) Medications known to lower the seizure threshold must be discontinued or substituted at least 4 weeks prior to study entry Agrees to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agrees to use a condom if he is having sex with a woman who is pregnant while on study drug 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 Exclusion Criteria: Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy) Prior use of ARN-509 (apalutamide) Have known allergies, hypersensitivity, or intolerance to ARN-509 (apalutamide) or its excipients Prior or ongoing systemic therapy for prostate cancer including, but not limited to: Hormonal therapy (e.g. leuprolide, goserelin, triptorelin) Cytochrome P450 (CYP)-17 inhibitors (e.g. abiraterone, ketoconazole) Antiandrogens (e.g. bicalutamide, nilutamide) Second generation antiandrogens (e.g. enzalutamide) Immunotherapy (e.g. sipuleucel-T, ipilimumab) Chemotherapy (e.g. docetaxel, cabazitaxel) Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements History of any of the following: 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) 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 Any condition that in the opinion of the investigator, would preclude participation in this study Current evidence of any of the following: Uncontrolled hypertension Gastrointestinal disorder affecting absorption Active infection (e.g. human immunodeficiency virus [HIV] or viral hepatitis) or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated Any condition that in the opinion of the investigator, would preclude participation in this study The 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) The use of strong CYP3A4 inhibitors, including: itraconazole, clarithromycin, erythromycin, diltiazem, verapamil, delavirdine, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice (or grapefruits) Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide Strong CYP3A4 inducers, including: phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, efavirenz, tipranavir, St. John's wort **Note: If a patient is on a strong CYP3A4 inhibitor, they can be reconsidered for enrollment if they can safely stop said medication; a two week or 5 half-lives, whichever is longer, washout will be required prior to enrolling on study; subject may not resume medication while receiving apalutamide Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (apalutamide)<br>Patients receive apalutamide PO QD for 90 days in the absence of disease progression or unacceptable toxicity. | Drug: Apalutamide<br>* Given PO<br>* Other names: JNJ-56021927;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative (i.e. no Residual Carcinoma) Site Directed and Systematic Prostate Biopsy Rate | Negative rate will be presented as the percent of subjects with a negative repeat biopsy, and will be calculated as: (number of patients with a negative biopsy following 90-days of apalutamide) / (total number of patients enrolled on the study) x 100. A 1-sample chi-square test will be used to compare the proportion with a negative repeat biopsy to the null hypothesis value of 20% (above). The 95% confidence interval will be computed. | At 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Exiting Active Surveillance Due to Pathologic Reclassification | The percentage of patients who exited active surveillance due to pathologic reclassification (e.g. increasing tumor volume or gleason score) will be computed along with its 95% confidence interval. | At 2 years | 
| Percentage of Patients Exiting Active Surveillance for Any Reason | Percentage of patients exiting active surveillance for any reason will be computed along with its 95% confidence interval. | At 2 years | 
| Percent of Men Undergoing Local Treatment | Computed along with its 95% confidence interval. | At 2 years | 
| Local Treatment Free Survival | Median treatment free survival will be estimated using Kaplan-Meier methods and 95% confidence interval will be calculated | Up to 730 days | 
| Prostate-specific Antigen Progression Rate | Prostate-specific antigen progression rate is the proportion of patients that had PSA progression following treatment. PSA progression is as a confirmed rising prostate-specific antigen >= 2 ng/mL, with subsequent PSA values obtained at least one week apart. | At 2 years | 
| Prostate-specific Antigen Progression Free Survival as Defined by the Prostate Cancer Working Group 2 Criteria | Prostate-specific antigen progression free survival will be estimated using Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula. | At 2 years | 
| Change in Radiographic Disappearance of Magnetic Resonance Imaging Detectable Prostate Cancer | This calculates the percentage of participants with radiographic disappearance of magnetic resonance imaging detectable prostate cancer. This is only in patients with a baseline nodule that is Prostate Imaging Reporting and Data System 3 or more and > 5 mm. | Baseline to up to 90 days | 
| Change in Quality of Life: FACT-P Assessment | As assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) surveys. Functional Assessment of Cancer Therapy-Prostate is a validated quality of life survey specific for patients with prostate cancer. The total FACT-P score ranges from 0 to 156, with higher scores indicating better quality of life. The change in FACT-P score between baseline and day 730 is reported. | Baseline compared to 730 days | 
| Change in Quality of Life: SF-36 Physical Functioning | As assessed using the Short Form-36 (SF-36) survey physical functioning subscale. Short Form-36 is a validated quality of life survey. This is a generic survey to assess an individual's overall well-being, and is not specific to one disease. The SF-36 physical functioning subscale score ranges from 0 to 100, with higher scores indicating better quality of life. The change in SF-36 energy/fatigue subscale score between baseline and day 730 is reported. | Baseline compared to 730 days | 
| Change in Quality of Life: SF-36 Energy/Fatigue | As assessed using the Short Form-36 (SF-36) survey energy/fatigue subscale. Short Form-36 is a validated quality of life survey. This is a generic survey to assess an individual's overall well-being, and is not specific to one disease. The SF-36 energy/fatigue subscale score ranges from 0 to 100, with higher scores indicating better quality of life. The change in SF-36 energy/fatigue subscale score between baseline and day 730 is reported. | Baseline compared to 730 days | 
| Change in Quality of Life: SF-36 Emotional Well Being | As assessed using the Short Form-36 (SF-36) survey emotional well being subscale. Short Form-36 is a validated quality of life survey. This is a generic survey to assess an individual's overall well-being, and is not specific to one disease. The SF-36 emotional well being subscale score ranges from 0 to 100, with higher scores indicating better quality of life. The change in SF-36 emotional well being subscale score between baseline and day 730 is reported. | Baseline compared to 730 days |