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

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ClinicalTrials.gov Identifier: NCT02721979
Recruitment Status : Recruiting
First Posted : March 29, 2016
Last Update Posted : March 14, 2019
Sponsor:
Collaborators:
Janssen Scientific Affairs, LLC
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE March 11, 2016
First Posted Date  ICMJE March 29, 2016
Last Update Posted Date March 14, 2019
Actual Study Start Date  ICMJE November 2, 2017
Estimated Primary Completion Date February 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
Negative (i.e. no residual carcinoma) site directed and systematic prostate biopsy rate [ Time Frame: At 90 days ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
Negative (i.e. no residual carcinoma) site directed and systematic prostate biopsy rate [ Time Frame: At 90 days ]
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 ARN-509) / (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 (CI) will be computed.
Change History Complete list of historical versions of study NCT02721979 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2019)
  • Alteration in MYC/chromosome 8q24 via fluorescence in situ hybridization [ Time Frame: Baseline to up to 91 days ]
    Fluorescence in situ hybridization will be conducted to assess for genomic alterations (loss or amplification) of the MYC gene, which is located on chromosome 8q24.
  • Change in quality of life as assessed using the Functional Assessment of Cancer Therapy-Prostate surveys [ Time Frame: Baseline to up to 730 days ]
    Functional Assessment of Cancer Therapy-Prostate is a validated quality of life survey specific for patients with prostate cancer.
  • Change in quality of life as assessed using the Short Form-36 survey [ Time Frame: Baseline to up to 730 days ]
    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.
  • Change in radiographic disappearance of magnetic resonance imaging detectable prostate cancer [ Time Frame: Baseline to up to 90 days ]
    Only in patients with a baseline nodule that is Prostate Imaging Reporting and Data System 3 or more and > 5 mm.
  • Incidence of adverse events [ Time Frame: Up to 730 days ]
    As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
  • Local treatment free survival [ Time Frame: Up to 730 days ]
    Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.
  • Percent of men undergoing of local treatment [ Time Frame: At 2 years ]
    Computed along with its 95% confidence interval.
  • Percentage of patients exiting active surveillance due to pathologic reclassification [ Time Frame: At 2 years ]
    Will be computed along with its 95% confidence interval.
  • Percentage of patients exiting active surveillance for any reason [ Time Frame: At 2 years ]
    Will be computed along with its 95% confidence interval.
  • Phosphatase and tensin homolog (PTEN) fluorescence in situ hybridization [ Time Frame: Baseline to up to 91 days ]
    Fluorescence in situ hybridization will be conducted to assess for genomic loss of the PTEN gene.
  • Prostate-specific antigen progression free survival as defined by the Prostate Cancer Working Group 2 criteria [ Time Frame: At 2 years ]
    Prostate-specific antigen progression free survival will be estimated using Kaplan-Meier methods and 95% confidence interval will be estimated using Greenwood's formula.
  • Prostate-specific antigen progression rate as defined by the Prostate Cancer Working Group 2 criteria (i.e. confirmed rising prostate-specific antigen >= 2 ng/mL at least one week apart) [ Time Frame: At 2 years ]
    Prostate-specific antigen progression rate will be computed along with 95% confidence interval.
  • PTEN immunohistochemistry [ Time Frame: Baseline to up to 91 days ]
    Immunohistochemistry will be conducted to assess for loss of PTEN protein expression.
  • Severity of adverse events [ Time Frame: Up to 730 days ]
    As assessed by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03.
  • Tumor messenger ribonucleic acid expression profiling/risk classification (e.g. Decipher or ribonucleic acid-seq) [ Time Frame: Baseline to up to 91 days ]
    Messenger ribonucleic acid expression profiling will be conducted using the Decipher assay and/or ribonucleic acid-seq.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Change in radiographic disappearance of MRI detectable prostate cancer (in patients with a baseline nodule that is PIRADS 3 or more and > 5 mm) [ Time Frame: Baseline to up to 90 days ]
  • Percentage of patients exiting active surveillance due to pathologic reclassification. [ Time Frame: At 2 years ]
  • Percentage of patients exiting active surveillance for any reason. [ Time Frame: At 2 years ]
  • Incidence of adverse events [ Time Frame: Up to 730 days ]
    As assessed by National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.03
  • Severity of adverse events [ Time Frame: Up to 730 days ]
    As assessed by National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.03
  • Local treatment free survival [ Time Frame: Up to 730 days ]
    Kaplan-Meier methods and 95% CI will be estimated using Greenwood's formula.
  • Percent of men undergoing of local treatment [ Time Frame: At 2 years ]
    Computed along with its 95% CI.
  • PSA PFS as defined by the PCWG2 criteria [ Time Frame: At 2 years ]
    PSA PFS will be estimated using Kaplan-Meier methods and 95% CI will be estimated using Greenwood's formula.
  • PSA progression rate as defined by the PCWG2 criteria (i.e. confirmed rising PSA >= 2 ng/mL at least one week apart) [ Time Frame: At 2 years ]
    PSA progression rate will be computed along with 95% CI.
  • Phosphatase and tensin homolog (PTEN) fluorescence in situ hybridization (FISH) [ Time Frame: Baseline to up to 91 days ]
    Fluorescence in situ hybridization will be conducted to assess for genomic loss of the PTEN gene.
  • PTEN immunohistochemistry (IHC) [ Time Frame: Baseline to up to 91 days ]
    Immunohistochemistry will be conducted to assess for loss of PTEN protein expression.
  • Alteration in MYC/chromosome 8q24 via FISH [ Time Frame: Baseline to up to 91 days ]
    Fluorescence in situ hybridization will be conducted to assess for genomic alterations (loss or amplification) of the MYC gene, which is located on chromosome 8q24.
  • Tumor mRNA expression profiling/risk classification (e.g. Decipher, or RNA-seq) [ Time Frame: Baseline to up to 91 days ]
    mRNA expression profiling will be conducted using the Decipher assay and/or RNA-seq.
  • Change in quality of life as assessed using the FACT-P survey [ Time Frame: Baseline to up to 730 days ]
    FACT-P is a validated quality of life survey specific for patients with prostate cancer
  • Change in quality of life as assessed using the SF36 survey [ Time Frame: Baseline to up to 730 days ]
    SF-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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apalutamide in Treating Patients With Prostate Cancer Who Are in Active Surveillance
Official Title  ICMJE A Phase 2 Study of Apalutamide in Active Surveillance Patients
Brief Summary 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

PRIMARY OBJECTIVES:

I. Determine the negative repeat biopsy rate by site directed and systematic prostate biopsy after 90-days of apalutamide.

SECONDARY OBJECTIVES:

I. Determine the rate of exit at 2 years from active surveillance due to pathologic reclassification.

II. Determine the overall rate of exit at 2 years from active surveillance.

III. Determine the rate of local treatment (e.g. radical prostatectomy, radiation therapy, brachytherapy) at 2 years and the local treatment free survival.

IV. Determine prostate-specific antigen (PSA) progression rates and PSA progression free survival (PFS), as defined by the Prostate Cancer Working Group 2 (PCWG2) criteria.

V. Determine the rate of radiographic disappearance of magnetic resonance imaging (MRI) detectable prostate cancer following treatment (only in patients with a baseline nodule that is Prostate Imaging Reporting and Data System [PIRADS] 3 or more and > 5 mm).

VI. Investigate the safety of apalutamide in men undergoing active surveillance; safety will be evaluated by the incidence, severity, duration, causality, seriousness, and type(s) of adverse events as assessed by the revised National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03 published 14 June 2010.

VII. Track quality of life utilizing the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form (SF)36 surveys for each cohort.

VIII. Exploratory biomarker assessment.

OUTLINE:

Patients receive apalutamide orally (PO) once daily (QD) for 90 days.

After completion of the study treatment, patients are followed up at 180, 365, 545, and 730 days.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Stage II Prostate Adenocarcinoma AJCC v7
Intervention  ICMJE
  • Drug: Apalutamide
    Given PO
    Other Names:
    • ARN 509
    • ARN-509
    • ARN509
    • JNJ 56021927
    • JNJ-56021927
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms  ICMJE Experimental: Treatment (apalutamide)
Patients receive apalutamide PO QD for 90 days.
Interventions:
  • Drug: Apalutamide
  • Other: Laboratory Biomarker Analysis
  • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 22, 2016)
33
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2, 2021
Estimated Primary Completion Date February 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 randomization
  • Platelet count >= 100,000 x 10^9/uL (at screening) independent of transfusion and/or growth factors within 3 months prior to randomization
  • 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 randomization, 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 randomization
    • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries Singapore
 
Administrative Information
NCT Number  ICMJE NCT02721979
Other Study ID Numbers  ICMJE 9582
NCI-2016-00221 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9582 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG1716037 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE
  • Janssen Scientific Affairs, LLC
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Michael Schweizer Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP