Back to resultsPerioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence (PeP-RALP)
Primary Purpose
Prostate Cancer
Status
Recruiting
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Propranolol
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer
Eligibility Criteria
Inclusion Criteria: European Association of Urology Intermediate- and High Risk for Biochemical recurrence and planned for curative RALP ECOG Performance Status 0-1 Exclusion Criteria: Medical Conditions Sick sinus syndrome Atrioventricular (AV) block grade 2 and 3 Recent (3 months) myocardial infarction Known unstable- or vasospastic- angina Heart failure (New York Heart Association [NYHA] > 2) Symptomatic peripheral vascular disease (e.g. intermittent claudication) Known pulmonary hypertension Known carotid artery stenosis or recent (3 months) stroke Bronchial asthma or other chronic obstructive pulmonary disease (COPD) Kidney failure (estimated Glomerular filtration rate [eGFR]<50) Liver failure (cirrhosis, jaundice, signs of hepatic decompression) Unregulated diabetes mellitus Untreated thyroid disorder Depressive episode within last 6 months (within last 12 months if major depressive episode) Known drug allergy against propranolol or excipients Any medical conditions considered to prohibit Propranolol use as judged by the treating physician (including frailty). Participants with known substance- or alcohol-abuse Prior/Concomitant Therapy Recent (<3 month) use of systemic beta-blockers prior to screening. Patients receiving non-dihydropyridine calcium channel blocking agents (eg diltiazem, verapamil) Patients receiving anti-arrhythmic agents (e.g. amiodarone, sotalol, digoxin, verapamil, flecainide) Patients receiving digoxin, rizatriptan, hydralazine, fluvoksamin, or fluoksetin Patients using daily anxiolytics (e.g. benzodiazepines), alpha-receptor adrenergic agonists (e.g. clonidine) Recommendations in the Summary of Product Characteristics for propranolol regarding concomitant use of other medications will be adhered to. Diagnostic assessments Sinus bradycardia (<60 beats/minute) Resting blood pressure <110/60mmHg OR hypertension BP >160/100 AV-block on ECG
Sites / Locations
- Oslo University Hospital The Norwegian Radium HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Propranolol
Placebo
Arm Description
Participants will receive Propranolol capsule for a period of 22-28 days, low dose (1 capsule/20mg propranolol twice daily) treatment the first- and last- three days of the treatment period. Higher dose (2 capsules/40mg propranolol twice daily) for the rest of the treatment period.
Participants will receive Propranolol capsule for a period of 22-28 days, low dose (1 capsule twice daily) treatment the first- and last- three days of the treatment period. Higher dose (2 capsules twice daily) for the rest of the treatment period.
Outcomes
Primary Outcome Measures
The feasibility of conducting a formal larger RCT to compare the efficacy of propranolol vs placebo to decrease PCa recurrence following RALP.
Numbers of eligible participants needed to screen to include 40 patients in the study, reported as % of eligible participants that subsequently were included in the study.
Compliance of study intervention (defined as >80% of doses taken). Reported as % of participants compliant to the study intervention before RALP and % of participants compliant to the study intervention after RALP.
Secondary Outcome Measures
Safety and tolerability of PeP-RALP intervention
Safety:
Proportion (%) of patients experiencing treatment related clinical significant hypotension and/or bradycardia.
Adverse events of PeP-RALP medication as assessed by CTCAE v5.0.
Tolerability:
Proportion (%) of patients tolerating daily dose of 80mg propranolol.
Determine the effect of RALP on catecholamine levels
Changes in catecholamine levels in the perioperative period.
Determine the bioavailability of propranolol
Serum levels of propranolol pre-operatively and at end of PeP-RALP medication.
Determine the effect of preoperative propranolol treatment on the serum level of PSA
Changes in PSA levels after 7-14 days of PeP-RALP medication.
To determine the effect of propranolol on post-operative biochemical failure
Proportion of patients with serum PSA levels above 0.1 ng/ml at 6 weeks post-RALP.
Intraoperative anesthesiological and surgical challenges Surgical complications in PeP RALP patients
Anesthesiological challenges are assed by:
Proportion of patients (%) in each intervention group requiring vasopressors to maintain an acceptable mean arterial pressure (MAP >60mmhg). Amount of vasopressor needed.
Surgical challenges are assed by:
The surgical procedure time (minutes) and estimated intraoperative blood loss (milliliters).
Surgical complications
Frequence (n=) and severity of surgical complications as classified by the Clavian-Dindo classification.
Full Information
NCT ID
NCT05679193
First Posted
December 12, 2022
Last Updated
February 8, 2023
Sponsor
Oslo University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05679193
Brief Title
Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence
Acronym
PeP-RALP
Official Title
Perioperative Propranolol in Robotic Assisted Laparoscopic Prostatectomy- A Feasibility Study of Propranolol to Target Perioperative Stress Induced Cancer Progression
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 2, 2023 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
October 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the feasibility of conducting a larger randomized controlled trial to assess the efficacy of perioperative propranolol capsules compared with placebo capsules in decreasing recurrence of prostate cancer after robotic assisted laparoscopic prostatectomy (RALP) in participants with intermediate to high-risk for prostate cancer recurrence.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
parallel-group, phase 2, double-blind, 2-arm study
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Propranolol
Arm Type
Experimental
Arm Description
Participants will receive Propranolol capsule for a period of 22-28 days, low dose (1 capsule/20mg propranolol twice daily) treatment the first- and last- three days of the treatment period. Higher dose (2 capsules/40mg propranolol twice daily) for the rest of the treatment period.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive Propranolol capsule for a period of 22-28 days, low dose (1 capsule twice daily) treatment the first- and last- three days of the treatment period. Higher dose (2 capsules twice daily) for the rest of the treatment period.
Intervention Type
Drug
Intervention Name(s)
Propranolol
Other Intervention Name(s)
Pranolol
Intervention Description
Propranolol capsules 20mg taken orally
Day: 1-3:
20mg twice daily
Day: 4-19 (25 , In cases of delayed RALP an extension of up to 6 days is allowed.in cases of delayed surgery).
2x 20mg twice daily
Day 20-22 20mg twice daily
Primary Outcome Measure Information:
Title
The feasibility of conducting a formal larger RCT to compare the efficacy of propranolol vs placebo to decrease PCa recurrence following RALP.
Description
Numbers of eligible participants needed to screen to include 40 patients in the study, reported as % of eligible participants that subsequently were included in the study.
Compliance of study intervention (defined as >80% of doses taken). Reported as % of participants compliant to the study intervention before RALP and % of participants compliant to the study intervention after RALP.
Time Frame
The feasability will be assessed after the 6-9 months. The total duration of study participation from screening to end of follow-up is 50-102 days per participant.
Secondary Outcome Measure Information:
Title
Safety and tolerability of PeP-RALP intervention
Description
Safety:
Proportion (%) of patients experiencing treatment related clinical significant hypotension and/or bradycardia.
Adverse events of PeP-RALP medication as assessed by CTCAE v5.0.
Tolerability:
Proportion (%) of patients tolerating daily dose of 80mg propranolol.
Time Frame
9 weeks
Title
Determine the effect of RALP on catecholamine levels
Description
Changes in catecholamine levels in the perioperative period.
Time Frame
Up to 5 weeks
Title
Determine the bioavailability of propranolol
Description
Serum levels of propranolol pre-operatively and at end of PeP-RALP medication.
Time Frame
Up to 5 weeks
Title
Determine the effect of preoperative propranolol treatment on the serum level of PSA
Description
Changes in PSA levels after 7-14 days of PeP-RALP medication.
Time Frame
7-14 days
Title
To determine the effect of propranolol on post-operative biochemical failure
Description
Proportion of patients with serum PSA levels above 0.1 ng/ml at 6 weeks post-RALP.
Time Frame
Up to 9 weeks
Title
Intraoperative anesthesiological and surgical challenges Surgical complications in PeP RALP patients
Description
Anesthesiological challenges are assed by:
Proportion of patients (%) in each intervention group requiring vasopressors to maintain an acceptable mean arterial pressure (MAP >60mmhg). Amount of vasopressor needed.
Surgical challenges are assed by:
The surgical procedure time (minutes) and estimated intraoperative blood loss (milliliters).
Time Frame
1 day
Title
Surgical complications
Description
Frequence (n=) and severity of surgical complications as classified by the Clavian-Dindo classification.
Time Frame
Up to 9 weeks
Other Pre-specified Outcome Measures:
Title
Change in perceived distress during the study.
Description
Investigate alterations in perioperative perceived distress, assessed by Hospital Anxiety and Depression Scale (HADS)
Time Frame
Up to 9 weeks
Title
Immunohistochemistry and Image mass cytometry of tumor to assess for differences between treatment arms. Flow cytometry to assess of periferal blood to assess for differences between treatment arms.
Description
Immunohistochemistry and image mass cytometry to assess for differences between treatment arms in intra-tumor immune cell infiltration.
Flow cytometry to assess differences between treament arms in systemic immune cell acitivity.
Time Frame
Up to 9 weeks
Title
Difference in prognostic markers (e.g. Decipher GRID transcriptome analysis) between treatment arms. Identify predictive biomarkers for propranolol responsiveness (e.g. Decipher GRID transcriptome analysis)
Description
Determine the effect of pre-operative propranolol treatment on prognostic markers and assess for predictive biomarkers. Identify predictive biomarkers for propranolol responsiveness.
Time Frame
up to 1 year
Title
Differences between intervention arms with regard to intraoperative alterations in cerebral autoregulation and intracranial pressure, measured by transcranial doppler (TCD) floe velocity.
Description
Intraoperative alterations in cerebral autoregulation and intracranial pressure by Transcranial Doppler flow velocity measurement of the middle cerebral artery.
Time Frame
up to 1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
European Association of Urology Intermediate- and High Risk for Biochemical recurrence and planned for curative RALP
ECOG Performance Status 0-1
Exclusion Criteria:
Medical Conditions
Sick sinus syndrome
Atrioventricular (AV) block grade 2 and 3
Recent (3 months) myocardial infarction
Known unstable- or vasospastic- angina
Heart failure (New York Heart Association [NYHA] > 2)
Symptomatic peripheral vascular disease (e.g. intermittent claudication)
Known pulmonary hypertension
Known carotid artery stenosis or recent (3 months) stroke
Bronchial asthma or other chronic obstructive pulmonary disease (COPD)
Kidney failure (estimated Glomerular filtration rate [eGFR]<50)
Liver failure (cirrhosis, jaundice, signs of hepatic decompression)
Unregulated diabetes mellitus
Untreated thyroid disorder
Depressive episode within last 6 months (within last 12 months if major depressive episode)
Known drug allergy against propranolol or excipients
Any medical conditions considered to prohibit Propranolol use as judged by the treating physician (including frailty).
Participants with known substance- or alcohol-abuse
Prior/Concomitant Therapy
Recent (<3 month) use of systemic beta-blockers prior to screening.
Patients receiving non-dihydropyridine calcium channel blocking agents (eg diltiazem, verapamil)
Patients receiving anti-arrhythmic agents (e.g. amiodarone, sotalol, digoxin, verapamil, flecainide)
Patients receiving digoxin, rizatriptan, hydralazine, fluvoksamin, or fluoksetin
Patients using daily anxiolytics (e.g. benzodiazepines), alpha-receptor adrenergic agonists (e.g. clonidine)
Recommendations in the Summary of Product Characteristics for propranolol regarding concomitant use of other medications will be adhered to.
Diagnostic assessments
Sinus bradycardia (<60 beats/minute)
Resting blood pressure <110/60mmHg OR hypertension BP >160/100
AV-block on ECG
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shivanthe Sivanesan, MD
Phone
48901218
Ext
0047
Email
shivants@uio.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shivanthe Sivanesan, MD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital The Norwegian Radium Hospital
City
Oslo
ZIP/Postal Code
4953
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shivanthe Sivanesan, MD
Email
shisiv@ous-hf.no
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence
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