Apalutamide and Leuprolide in Intermediate and High-risk Prostate Cancer

Sponsor
Case Comprehensive Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT02770391
Collaborator
(none)
54
1
1
42.4
1.3

Study Details

Study Description

Brief Summary

This is a research study to test an investigational drug (Not FDA approved), Apalutamide given in combination with Leuprolide acetate (FDA approved) in men diagnosed with high-risk prostate cancer who have already selected to have surgery to remove their prostate gland as part of their treatment plan. The main purpose of this study is to determine how tumors make androgens (male hormones), which makes these tumors more aggressive and resistant to hormonal therapy and how a short period of treatment with Apalutamide and leuprolide acetate prior to surgery can affect the production of these hormones in normal and malignant prostate tissue.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Primary Objective: To evaluate the differential effect of neo-adjuvant leuprolide and Apalutamide on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.

Secondary Objective(s): To evaluate the differential effect of neoadjuvant leuprolide and Apalutamide on other androgen (testosterone (T), dehydroepiandrosterone (DHEA), androstenediol, 5α-androstanedione (5α-dione), androstenedione (AD), androsterone and 5α-androstanediol) concentrations in benign and malignant prostate tissue based on HSD3B1 genotype.

To compare the level of DHT, T, DHEA, androstenediol, 5α-dione, AD, androsterone and 5α-androstanediol between normal and malignant prostate tissue after neoadjuvant treatment with leuprolide and Apalutamide

To determine the safety of the combination of Leuprolide and Apalutamide administered prior to radical prostatectomy

To evaluate prostatic specific antigen (PSA), FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR)) in benign and malignant prostate tissue after treatment with Leuprolide and Apalutamide.

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The Association Between HSD3B1 Genotype and Steroid Metabolism in Normal and Prostate Cancer Tissue of Men With Intermediate and High-risk Prostate Cancer Undergoing Radical Prostatectomy After Treatment With Apalutamide and Leuprolide
Actual Study Start Date :
Oct 17, 2016
Actual Primary Completion Date :
Apr 29, 2020
Actual Study Completion Date :
Apr 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Apalutamide + Leuprolide Acetate

All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before

Drug: Leuprolide acetate
Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
Other Names:
  • Lupron
  • Drug: Apalutamide
    Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection.
    Other Names:
  • ARN-509
  • Procedure: Radical prostatectomy

    Outcome Measures

    Primary Outcome Measures

    1. Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status [Up to 28 Days]

      To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.

    2. Dihydrotestosterone (DHT) Concentration in Malignant Prostate Tissue After a Combination Drug Treatment Based on Genotype Status [Up to 28 Days]

      To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in malignant prostate tissue based on HSD3B1 genotype.

    Secondary Outcome Measures

    1. Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate the differential effect of neoadjuvant leuprolide and ARN-509 on other androgens (testosterone (T), dehydroepiandrosterone (DHEA), androstenediol, 5?-androstanedione (5?-dione), androstenedione (AD), androsterone and 5?-androstanediol) concentration in benign prostate tissue based on HSD3B1 genotype.

    2. Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate the effect of neoadjuvant ARN-509 on other androgens (DHT, T, DHEA, androstenediol, 5?-dione, AD, androsterone and 5?-androstanediol) concentration in malignant prostate tissue after neoadjuvant leuprolide and ARN-509.

    3. To Compare the Level of DHT, T, DHEA, Androstenediol, 5alpha-dione, AD, Androsterone and 5alpha-androstanediol Between Normal and Malignant Prostate Tissue After Neoadjuvant Leuprolide and ARN-509. [Up to 28 Days]

      To compare the level of DHT, T, DHEA, androstenediol, 5alpha-dione, AD, androsterone and 5alpha-androstanediol between normal and malignant prostate tissue after neoadjuvant leuprolide and ARN-509.

    4. PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via IHC) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.

    5. PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via qPCR) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.

    6. PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via IHC) in benign prostate tissue after treatment with Leuprolide and Apalutamide.

    7. PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status. [Up to 28 Days]

      To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via qPCR) in benign prostate tissue after treatment with Leuprolide and Apalutamide.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Adenocarcinoma of the prostate with histological or cytological confirmation without neuroendocrine differentiation or small cell histology and with G 4+3 or higher, and PSA ≥ 10, and ≥T2b, for whom radical prostatectomy has been recommended and who choose to undergo radical prostatectomy.

    • A minimum tissue requirement of ≥3 core biopsies with tumor involvement and at least 50% tumor involvement in one of the core biopsies is required.

    • Have an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    • Hemoglobin of ≥ 10 g/dL, independent of transfusion and/or growth factors within 3 months prior to randomization

    • Platelet count of ≥ 100k/mL independent of transfusion and/or growth factors within 3 months prior to randomization

    • Serum albumin ≥3.0 g/dL

    • Serum creatinine < 2.0 times the upper limit of normal (ULN) {or a calculated creatinine clearance ≥ 60 mL/min}

    • Serum potassium ≥3.5 mmol/L

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN

    • Total serum bilirubin levels < 1.5 x ULN (Note: In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject may be eligible)

    • Be capable of swallowing study agents whole as a tablet

    • Be willing/able to adhere to the prohibitions and restrictions specified in this protocol

    • Have signed an informed consent document indicating that the subject understands the purpose of and procedures required for the study and are willing to participate in the study.

    • 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 following the last dose of study drug.

    Exclusion Criteria:
    • The use of any prior hormones including luteinizing hormone-releasing hormone (LHRH) agonists , LHRH antagonists, antiandrogens such as bicalutamide, flutamide and nilutamide, and/or the use of 5-alpha reductase inhibitors, prostate cancer (PC) Spes (or PC-x product), Megestrol Acetate, or estrogen containing nutriceuticals within 6 months of study treatment initiation.

    • Prior radiation therapy, immunotherapy, chemotherapy or other investigational therapy given for prostate cancer.

    • "Currently active" second malignancy other than non-melanoma skin cancers or non-muscle invasive transitional cell carcinoma of bladder. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse.

    • History of seizure or 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)

    • Current systemic steroid therapy (inhaled or topical steroids are also not allowed)

    • Have received treatment with any form of therapy with CYP17 inhibitory activity such as ketoconazole, aminoglutethimide, or an antiandrogen such as bicalutamide within 6 months of study treatment initiation.

    • Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids within 6 months of enrollment

    • Active infection (eg, human immunodeficiency virus [HIV] or viral hepatitis)

    • Have uncontrolled hypertension;subjects with a history of hypertension are permitted in the study provided their blood pressure is controlled by anti-hypertensive therapy, at the discretion of the treating physician

    • Have a known history of pituitary or adrenal dysfunction

    • Have clinically significant heart disease as evidenced by 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

    • Have a history of gastric bypass surgery or severe malabsorption that may interfere with the absorption of the study agents

    • Be taking or require the use of prohibited medications as listed

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cleveland Clinic, Case Comprehensive Cancer Center Cleveland Ohio United States 44195

    Sponsors and Collaborators

    • Case Comprehensive Cancer Center

    Investigators

    • Principal Investigator: Moshe Ornstein, MD, Cleveland Clinic, Case Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Moshe Ornstein, MD, Case Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02770391
    Other Study ID Numbers:
    • CASE5815
    First Posted:
    May 12, 2016
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Moshe Ornstein, MD, Case Comprehensive Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Period Title: Overall Study
    STARTED 54
    COMPLETED 48
    NOT COMPLETED 6

    Baseline Characteristics

    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Overall Participants 54
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    26
    48.1%
    >=65 years
    28
    51.9%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    Male
    54
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    53
    98.1%
    Unknown or Not Reported
    1
    1.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    1.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    5
    9.3%
    White
    46
    85.2%
    More than one race
    0
    0%
    Unknown or Not Reported
    2
    3.7%

    Outcome Measures

    1. Primary Outcome
    Title Dihydrotestosterone (DHT) Concentration in Benign Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
    Description To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in benign prostate tissue based on HSD3B1 genotype.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue each gave two samples
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 15
    Measure Tissue Sample 30
    homozygous (1245A)
    9.066
    (7.775)
    heterozygous (1254C)
    5.917
    (3.458)
    homozygous (1245C)
    9.345
    (5.607)
    2. Secondary Outcome
    Title Other Androgens Concentration in Benign Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate the differential effect of neoadjuvant leuprolide and ARN-509 on other androgens (testosterone (T), dehydroepiandrosterone (DHEA), androstenediol, 5?-androstanedione (5?-dione), androstenedione (AD), androsterone and 5?-androstanediol) concentration in benign prostate tissue based on HSD3B1 genotype.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue gave two samples
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 15
    Measure Tissue Sample 30
    DHT homozygous(1245A)
    9.066
    (7.775)
    T homozygous(1245A)
    6.901
    (2.372)
    DHEA homozygous(1245A)
    46.110
    (82.578)
    AD homozygous(1245A)
    8.394
    (2.168)
    DHT heterozygous
    5.917
    (3.458)
    T heterozygous
    4.929
    (1.285)
    DHEA heterozygous
    18.5788
    (13.02)
    AD heterozygous
    6.083
    (2.5522)
    DHT homozygous (1245C)
    9.345
    (5.607)
    T homozygous (1245C)
    4.704
    (4.166)
    AD homozygous (1245C)
    8.303
    (2.841)
    3. Secondary Outcome
    Title Other Androgens (DHT, T, DHEA, Androstenediol, 5α-dione, AD, Androsterone and 5α-androstanediol) Concentration in Malignant Prostate Tissue After Neo-adjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate the effect of neoadjuvant ARN-509 on other androgens (DHT, T, DHEA, androstenediol, 5?-dione, AD, androsterone and 5?-androstanediol) concentration in malignant prostate tissue after neoadjuvant leuprolide and ARN-509.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue gave two samples
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 24
    Measure Tissue Sample 48
    DHT homozygous (1245A)
    8.855
    (7.4847)
    T homozygous (1245A)
    5.691
    (2.531)
    DHEA homozygous (1245A)
    22.941
    (11.523)
    AD homozygous (1245A)
    7.974
    (4.005)
    DHT heterozygous
    5.238
    (3.822)
    T heterozygous
    5.719
    (3.513)
    DHEA heterozygous
    24.543
    (16.779)
    AD heterozygous
    8.593
    (3.736)
    DHT homozygous (1245C)
    2.622
    (1.530)
    T homozygous (1245C)
    4.489
    (1.197)
    DHEA homozygous (1245C)
    1.421
    (0)
    AD homozygous (1245C)
    6.959
    (3.956)
    4. Secondary Outcome
    Title To Compare the Level of DHT, T, DHEA, Androstenediol, 5alpha-dione, AD, Androsterone and 5alpha-androstanediol Between Normal and Malignant Prostate Tissue After Neoadjuvant Leuprolide and ARN-509.
    Description To compare the level of DHT, T, DHEA, androstenediol, 5alpha-dione, AD, androsterone and 5alpha-androstanediol between normal and malignant prostate tissue after neoadjuvant leuprolide and ARN-509.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Insufficent Tissue
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 54
    Measure Tissue Sample 0
    5. Secondary Outcome
    Title PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via IHC) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue for PSA and H3K27 were Analyzed. Two samples collected per participant. There was insufficient tissue for TMPRSS2, EZH2, H3K27, and UBE2C expression.
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 39
    Measure Tissue Sample 78
    PSA Homozygous (1245A)
    1.15
    (0.662)
    H3K27 Homozygous (1245A)
    1.619
    (0.882)
    PSA heterozygous
    1.393
    (0.786)
    H3K27 heterozygous
    1.633
    (0.890)
    PSA Homozygous (1245C)
    1.375
    (1.500)
    H3K27 Homozygous (1245C)
    0.744
    (0.756)
    6. Secondary Outcome
    Title PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Malignant Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C tissue expression (via qPCR) in malignant prostate tissue after treatment with Leuprolide and Apalutamide.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue for PSA, FKBP5, TMPRSS2 were analyzed. Two samples were collected from each participant. There was insufficient tissues for the EZH2, H3K27, and UBE2C expression.
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 39
    Measure Tissue Sample 78
    PSA homozygous (1245A)
    1.474
    (1.488)
    FKBP5 homozygous (1245A)
    1.304
    (0.874)
    TMPRSS2 homozygous (1245A)
    1.603
    (1.071)
    PSA heterozygous
    1.127
    (1.109)
    FKBP5 heterozygous
    1.127
    (1.109)
    TMPRSS2 heterozygous
    1.742
    (1.790)
    PSA homozygous (1245C)
    2.221
    (1.027)
    FKBP5 homozygous (1245C)
    2.221
    (1.027)
    TMPRSS2 homozygous (1245C)
    2.345
    (1.145)
    7. Secondary Outcome
    Title PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via IHC) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via IHC) in benign prostate tissue after treatment with Leuprolide and Apalutamide.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Insufficient tissue
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 54
    Measure Tissue Sample 0
    8. Secondary Outcome
    Title PSA, FKBP5, TMPRSS2, EZH2, H3K27, and UBE2C Expression (Via qPCR) in Benign Prostate Tissue After Neoadjuvant Leuprolide and Apalutamide Based on Genotype Status.
    Description To evaluate PSA, FKBP5, TMPRSS2, EZH2, H3K27 and UBE2C tissue expression (via qPCR) in benign prostate tissue after treatment with Leuprolide and Apalutamide.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Insufficient Tissue
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 0
    9. Primary Outcome
    Title Dihydrotestosterone (DHT) Concentration in Malignant Prostate Tissue After a Combination Drug Treatment Based on Genotype Status
    Description To evaluate the differential effect of neo-adjuvant leuprolide and ARN-509 on dihydrotestosterone (DHT) concentration in malignant prostate tissue based on HSD3B1 genotype.
    Time Frame Up to 28 Days

    Outcome Measure Data

    Analysis Population Description
    Participants with sufficient tissue each gave two samples
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    Measure Participants 24
    Measure Tissue Sample 48
    homozygous (1245A)
    8.855
    (7.4847)
    heterozygous (1254C)
    5.238
    (3.822)
    homozygous (1245C)
    2.622
    (1.530)

    Adverse Events

    Time Frame Up to 8 Weeks following the last dose of study drug
    Adverse Event Reporting Description
    Arm/Group Title Apalutamide + Leuprolide Acetate
    Arm/Group Description All participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to Apalutamide 240 mg orally daily for four weeks prior to radical prostatectomy (RP). Treatment will be started on day (-28) ± 3 from the scheduled RP date to minimize the variability of treatment duration. Apalutamide may be continued up to and including the day before Leuprolide acetate: Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3 Apalutamide: Apalutamide, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. Apalutamide will be initiated the same day patients receive their leuprolide acetate injection. Radical prostatectomy
    All Cause Mortality
    Apalutamide + Leuprolide Acetate
    Affected / at Risk (%) # Events
    Total 0/54 (0%)
    Serious Adverse Events
    Apalutamide + Leuprolide Acetate
    Affected / at Risk (%) # Events
    Total 1/54 (1.9%)
    Reproductive system and breast disorders
    Genital Edema 1/54 (1.9%)
    Other (Not Including Serious) Adverse Events
    Apalutamide + Leuprolide Acetate
    Affected / at Risk (%) # Events
    Total 47/54 (87%)
    Blood and lymphatic system disorders
    Anemia 3/54 (5.6%)
    Endocrine disorders
    Hypothyroidism 9/54 (16.7%)
    Eye disorders
    Eye disorders - Other, specify (Intermittent dry & watering eyes) 1/54 (1.9%)
    Gastrointestinal disorders
    Bloating 1/54 (1.9%)
    Constipation 1/54 (1.9%)
    Diarrhea 5/54 (9.3%)
    Dry mouth 1/54 (1.9%)
    Nausea 4/54 (7.4%)
    General disorders
    Edema, face 1/54 (1.9%)
    Facial pain 1/54 (1.9%)
    Fatigue 29/54 (53.7%)
    Localized edema 1/54 (1.9%)
    Infections and infestations
    Upper respiratory infection 1/54 (1.9%)
    Investigations
    Alanine aminotransferase increased 5/54 (9.3%)
    Aspartate aminotransferase increased 6/54 (11.1%)
    Creatinine Increased 4/54 (7.4%)
    Hyperglycemia 5/54 (9.3%)
    Hyperkalemia 4/54 (7.4%)
    Hypernatremia 3/54 (5.6%)
    Hypoalbuminemia 2/54 (3.7%)
    Hyponatremia 1/54 (1.9%)
    Lymphocyte Count Decreased 5/54 (9.3%)
    Platelet count decreased 1/54 (1.9%)
    Weight Loss 2/54 (3.7%)
    White blood cell decreased 3/54 (5.6%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/54 (13%)
    Myalgia 2/54 (3.7%)
    Pain in extremity 2/54 (3.7%)
    Nervous system disorders
    Cognitive Disturbance 3/54 (5.6%)
    Cognitive Impairment 1/54 (1.9%)
    Dizziness 6/54 (11.1%)
    Dysgeusia 8/54 (14.8%)
    Headache 9/54 (16.7%)
    Nervous system disorders - Other, specify (Restless leg syndrome (6); Mental fogginess (2)) 8/54 (14.8%)
    Paresthesia 2/54 (3.7%)
    Psychiatric disorders
    Agitation 2/54 (3.7%)
    Anxiety 1/54 (1.9%)
    Depression 1/54 (1.9%)
    Insomnia 8/54 (14.8%)
    Libido decrease 3/54 (5.6%)
    Psychiatric disorders - Other, specify (Flat affect) 1/54 (1.9%)
    Restlessness 1/54 (1.9%)
    Renal and urinary disorders
    Dysuria 1/54 (1.9%)
    Urinary Frequency 4/54 (7.4%)
    Urinary Retention 1/54 (1.9%)
    Reproductive system and breast disorders
    Breast Pain 2/54 (3.7%)
    Erectile dysfunction 1/54 (1.9%)
    Prostatic obstruction 1/54 (1.9%)
    Reproductive system and breast disorders - Other, specify (Penis shrinkage) 1/54 (1.9%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 1/54 (1.9%)
    Cough 3/54 (5.6%)
    Skin and subcutaneous tissue disorders
    Alopecia 1/54 (1.9%)
    Erythema multiforme 1/54 (1.9%)
    Hyperhidrosis 1/54 (1.9%)
    Pruritus 6/54 (11.1%)
    Rash acneiform 1/54 (1.9%)
    Rash maculo-papular 5/54 (9.3%)
    Skin and subcutaneous tissue disorders - Other, specify (Skin disorder (2)) 2/54 (3.7%)
    Vascular disorders
    Hot Flashes 28/54 (51.9%)
    Hypertension 4/54 (7.4%)
    Hypotension 1/54 (1.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Moshe Ornstein,
    Organization Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
    Phone 18662238100
    Email taussigresearch@ccf.org
    Responsible Party:
    Moshe Ornstein, MD, Case Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02770391
    Other Study ID Numbers:
    • CASE5815
    First Posted:
    May 12, 2016
    Last Update Posted:
    Jun 21, 2022
    Last Verified:
    May 1, 2022