Clinical Trials /

ARN-509 and Leuprolide in Intermediate and High-risk Prostate Cancer

NCT02770391

Description:

This is a research study to test an investigational drug (Not FDA approved), ARN-509 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 ARN-509 and leuprolide acetate prior to surgery can affect the production of these hormones in normal and malignant prostate tissue.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ARN-509 and Leuprolide in Intermediate and High-risk Prostate Cancer
  • 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 ARN-509 and Leuprolide

Clinical Trial IDs

  • ORG STUDY ID: CASE5815
  • NCT ID: NCT02770391

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Leuprolide acetateLupronARN-509 + Leuprolide Acetate
ARN-509ARN-509 + Leuprolide Acetate

Purpose

This is a research study to test an investigational drug (Not FDA approved), ARN-509 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 ARN-509 and leuprolide acetate prior to surgery can affect the production of these hormones in normal and malignant prostate tissue.

Detailed Description

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

      Secondary Objective(s): To evaluate the differential effect of neoadjuvant leuprolide and
      ARN-509 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 ARN-509

      To determine the safety of the combination of Leuprolide and ARN-509 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 ARN-509 and
      ARN-509.
    

Trial Arms

NameTypeDescriptionInterventions
ARN-509 + Leuprolide AcetateExperimentalAll participating patients will receive a single dose of leuprolide 7.5 mg intramuscularly (IM) in addition to ARN-509 240 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. ARN-509 will be continued till the day of RP.
  • Leuprolide acetate
  • ARN-509

Eligibility Criteria

        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.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:dihydrotestosterone (DHT) concentration in benign prostate tissue after a combination drug treatment based on genotype status
Time Frame:Up to 28 Days
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • HSD3B1 Genotype
  • Steroid Metabolism
  • High-risk Prostate Cancer
  • ARN-509

Last Updated

February 19, 2019