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Beta Adrenergic Receptor Blockade as a Novel Therapy for Patients With Adenocarcinoma of the Prostate

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: NCT02944201
Recruitment Status : Recruiting
First Posted : October 25, 2016
Last Update Posted : January 23, 2020
Sponsor:
Collaborator:
Albert Einstein College of Medicine
Information provided by (Responsible Party):
Benjamin Gartrell, Montefiore Medical Center

Tracking Information
First Submitted Date  ICMJE October 21, 2016
First Posted Date  ICMJE October 25, 2016
Last Update Posted Date January 23, 2020
Actual Study Start Date  ICMJE April 1, 2017
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
Change in Biomarkers in Prostate Biopsy Compared to Prostatectomy Tissues [ Time Frame: 28 days after beginning carvedilol ]
BIomarker
Original Primary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
Change in Biomarkers in Prostate Biopsy Compared to Prostatectomy Tissues [ Time Frame: 28 days after beginning carvedilol ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2017)
Change in Serum PSA [ Time Frame: 28 days after beginning carvedilol ]
PSA
Original Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2016)
Change in Serum PSA [ Time Frame: 28 days after beginning carvedilol ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Beta Adrenergic Receptor Blockade as a Novel Therapy for Patients With Adenocarcinoma of the Prostate
Official Title  ICMJE Beta Adrenergic Receptor Blockade as a Novel Therapy for Patients With Adenocarcinoma of the Prostate
Brief Summary This will be a single arm, window of opportunity study in men with treatment-naïve prostate cancer who will proceed to prostatectomy. Men will be treated with carvedilol prior to undergoing prostatectomy.
Detailed Description

Preclinical research has demonstrated that autonomic nerve fibers in the prostate gland regulate prostate cancer development and dissemination. Studies in human prostate cancer specimens indicate that higher densities of autonomic nerve fibers are associated with poor clinical outcomes.

In this clinical trial the beta-blocker carvedilol will be given to men diagnosed with prostate cancer. Men will begin carvedilol following their diagnostic prostate biopsy and will continue carvedilol until prostatectomy. The primary outcome measure is the change in Ki-67 and TUNEL assay biomarkers in prostate biopsy and prostatectomy tissues.

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: Carvedilol
Carvedilol will give twice daily until prostatectomy
Other Name: Coreg
Study Arms  ICMJE Experimental: Carvedilol
Carvedilol will be started at 6.25 mg by mouth twice daily. Patients will take carvedilol for 28 days prior to prostatectomy. They will be seen every 7 days and adjustments in the dose will be considered at those visits.
Intervention: Drug: Carvedilol
Publications * Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, Frenette PS. Autonomic nerve development contributes to prostate cancer progression. Science. 2013 Jul 12;341(6142):1236361. doi: 10.1126/science.1236361.

*   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: October 21, 2016)
22
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. The patient must be able to provide study-specific informed consent prior to study entry.
  2. Age ≥ 18
  3. ECOG Performance Status 0-1
  4. Pathologically proven diagnosis of prostate adenocarcinoma diagnosed by prostate biopsy with archival biopsy tissue available for analysis. The amount of cancer tissue present must be sufficient for analysis.
  5. Prostate adenocarcinoma classified as intermediate or high-risk as defined by one or more of the following criteria: PSA >10 ng/ml, Gleason score ≥7, or tumor stage ≥T2b
  6. Patients must have no evidence of metastatic disease (including clinically negative pelvic lymph nodes) as established by imaging (CT or MRI of the pelvis and a bone scan) within 60 days prior to registration. Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis.
  7. The patient and the attending urologist have decided to proceed with prostatectomy
  8. Lab values meeting the following criteria

    1. Total bilirubin < 2.0 X Upper Limit of Normal (ULN)
    2. Aspartate aminotransferase (AST) ≤ 2.5 X ULN.
    3. Alanine aminotransferase (ALT ) ≤ 2.5 X ULN
    4. Absolute Neutrophil Count (ANC) > 1.5 K/mm3
    5. Platelets > 100 K/mm3
    6. Hemoglobin ≥9.0 g/dL
    7. calculated creatinine clearance ≥ 40 mL/min

    Exclusion Criteria:

  9. Patients with low risk prostate adenocarcinoma as defined by meeting all three of the following criteria: Gleason score ≤6, PSA <10 and tumor stage ≤T2b
  10. The presence of metastatic disease including to pelvic lymph nodes
  11. Use of any beta-blocker at the time of diagnostic biopsy for prostate cancer or use of any beta-blocker at the time of screening. If the investigator does not believe that carvedilol can be safely added to the patients existing antihypertensive regimen, then the patient is not eligible for this study.
  12. Prior therapy for prostate cancer including radiation therapy (external beam or brachytherapy), surgery, high-intensity focused ultrasound (HIFU), cryotherapy, previous hormonal therapy with androgen deprivation therapy by bilateral orchiectomy or LHRH analogues (e.g. leuprolide, goserelin, triptorelin, degarelix), antiandrogens, ketoconazole, abiraterone or chemotherapy (for prostate cancer, chemotherapy in the past for other indications is allowed).
  13. Treatment with any investigational agent within 30 days prior to being registered for protocol therapy.
  14. No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 5 years.
  15. Inability to take oral medication
  16. Hypotension (systolic blood pressure <100 mm Hg or diastolic blood pressure <50 mm Hg) or bradycardia (pulse <55 beats/min) at screening. For patients with a functioning pacemaker, bradycardia is not an exclusion.
  17. Bronchial asthma or related bronchospastic conditions such as chronic obstructive pulmonary disease.
  18. Patients must not have New York Heart Association Class III or IV heart failure at the time of screening. Patients must not have any unstable angina, myocardial infarction, or serious uncontrolled cardiac arrhythmia within 6 months prior to registration.
  19. Prolonged QTc interval on pre-entry 12-lead ECG (> 460 msec), obtained within 28 days prior to being registered on study. No second- or third-degree atrioventricular block on screening 12-lead ECG.
  20. Any other serious illness or medical condition that the principal investigator feels would make the patient a poor candidate for this study
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: Benjamin Gartrell, MD 718-405-8404 bgartrel@montefiore.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02944201
Other Study ID Numbers  ICMJE 2016-6632
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
Plan to Share IPD: No
Responsible Party Benjamin Gartrell, Montefiore Medical Center
Study Sponsor  ICMJE Montefiore Medical Center
Collaborators  ICMJE Albert Einstein College of Medicine
Investigators  ICMJE Not Provided
PRS Account Montefiore Medical Center
Verification Date January 2020

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