PeP-RALP: Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Propranolol 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. |
Drug: Propranolol
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
Other Names:
|
| Placebo Comparator: Placebo 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. |
Drug: Propranolol
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
Other Names:
|
Outcome Measures
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. [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.]
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 [9 weeks]
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 [Up to 5 weeks]
Changes in catecholamine levels in the perioperative period.
- Determine the bioavailability of propranolol [Up to 5 weeks]
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 [7-14 days]
Changes in PSA levels after 7-14 days of PeP-RALP medication.
- To determine the effect of propranolol on post-operative biochemical failure [Up to 9 weeks]
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 [1 day]
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 [Up to 9 weeks]
Frequence (n=) and severity of surgical complications as classified by the Clavian-Dindo classification.
Other Outcome Measures
- Change in perceived distress during the study. [Up to 9 weeks]
Investigate alterations in perioperative perceived distress, assessed by Hospital Anxiety and Depression Scale (HADS)
- 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. [Up to 9 weeks]
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.
- 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) [up to 1 year]
Determine the effect of pre-operative propranolol treatment on prognostic markers and assess for predictive biomarkers. Identify predictive biomarkers for propranolol responsiveness.
- Differences between intervention arms with regard to intraoperative alterations in cerebral autoregulation and intracranial pressure, measured by transcranial doppler (TCD) floe velocity. [up to 1 year]
Intraoperative alterations in cerebral autoregulation and intracranial pressure by Transcranial Doppler flow velocity measurement of the middle cerebral artery.
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Oslo University Hospital
Investigators
- Principal Investigator: Shivanthe Sivanesan, MD, Oslo University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 488466