Clinical Trials /

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

NCT02944201

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Beta Adrenergic Receptor Blockade as a Novel Therapy for Patients With Adenocarcinoma of the Prostate
  • Official Title: Beta Adrenergic Receptor Blockade as a Novel Therapy for Patients With Adenocarcinoma of the Prostate

Clinical Trial IDs

  • ORG STUDY ID: 2016-6632
  • NCT ID: NCT02944201

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
CarvedilolCoregCarvedilol

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
CarvedilolExperimentalCarvedilol 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.
  • Carvedilol

Eligibility Criteria

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

Primary Outcome Measures

Measure:Change in Biomarkers in Prostate Biopsy Compared to Prostatectomy Tissues
Time Frame:28 days after beginning carvedilol
Safety Issue:
Description:BIomarker

Secondary Outcome Measures

Measure:Change in Serum PSA
Time Frame:28 days after beginning carvedilol
Safety Issue:
Description:PSA

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Montefiore Medical Center

Trial Keywords

  • carvedilol
  • biomarkers
  • autonomic nerves

Last Updated

February 12, 2019