Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02770391
Recruitment Status : Recruiting
First Posted : May 12, 2016
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
Moshe Ornstein, Case Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE May 5, 2016
First Posted Date  ICMJE May 12, 2016
Last Update Posted Date May 6, 2020
Actual Study Start Date  ICMJE October 17, 2016
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
dihydrotestosterone (DHT) concentration in benign prostate tissue after a combination drug treatment based on genotype status [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ARN-509 and Leuprolide in Intermediate and High-risk Prostate Cancer
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Leuprolide acetate
    Leuprolide acetate, Intramuscular injection - 7.5 mg, one time dose on day (-28) ± 3
    Other Name: Lupron
  • Drug: ARN-509
    ARN-509, PO, 240 mg daily, starting day (-28) ± 3 until the day before radical prostatectomy. ARN-509 will be initiated the same day patients receive their leuprolide acetate injection.
  • Procedure: Radical prostatectomy
Study Arms  ICMJE Experimental: ARN-509 + Leuprolide Acetate
All 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.
Interventions:
  • Drug: Leuprolide acetate
  • Drug: ARN-509
  • Procedure: Radical prostatectomy
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: May 10, 2016)
57
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2020
Estimated Primary Completion Date October 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Moshe Ornstein, MD 1-866-223-8100 CancerCenterResearch@ccf.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02770391
Other Study ID Numbers  ICMJE CASE5815
Has Data Monitoring Committee Yes
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 Moshe Ornstein, Case Comprehensive Cancer Center
Study Sponsor  ICMJE Case Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Moshe Ornstein, MD Cleveland Clinic, Case Comprehensive Cancer Center
PRS Account Case Comprehensive Cancer Center
Verification Date May 2020

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