A Phase 2 interventional study of Propranolol in Prostate Cancer, sponsored by Oslo University Hospital. Completed at 1 site in Norway. Open to male participants aged 40 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-05-29.
Sponsored by Oslo University Hospital · Phase 2, Interventional, and Treatment
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 (PCa) after robotic assisted laparoscopic prostatectomy (RALP) in participants with intermediate to high-risk for prostate cancer recurrence.
PCa is the most commonly diagnosed cancer in Norway (2020) and RALP is the most frequent curative treatment offered to men with non-metastatic PCa. Biochemical recurrence (BCR) is estimated to occur to 40% of patients with EAU IR and HR PCa. Attempts to combat the high recurrence rates after RALP with neoadjuvant treatment, aiming to reduce the local tumor burden and treat possible micrometastasis, has of yet not proven beneficial.
The prostate is highly innervated and recent evidence has shown the importance of nerves in the development and progression of PCa. The action of particularly adrenergic nerves, in sum lead to a pro-cancerous and metastatic state by influencing key hallmarks of cancer like apoptosis resistance, angiogenesis, immune suppression, invasiveness and metastasis.
Perioperative stress caused by the cancer surgery, in this case RALP, has been found to promote cancer progression and recurrence both by enhancing growth of preexisting residual tumor/micrometastasis and facilitating formation of new metastasis. The surgical stress response cause a catecholamine-induced cancer progression where β2-adrenergic receptor (ADRB2) have a key role.
Our newly published pharma co-epidemiologic study indicate perioperative stress can be targeted by a non-selective ß-blocker (nsBB) like propranolol [1]. RCTs have found perioperative administration of propranolol alone, or in conjunction with COX-2 inhibition, to be safe and to reduce biomarkers associated with poor prognosis compared with the control group receiving placebo medication in patients undergoing radical surgery for breast-, ovarian- and colorectal cancer [2-7}.
The result of our register study, together with existing evidence of an effect of propranolol/nsBBs, provides foundation for PeP-RALP, a pilot study to establish the recruitment- and infrastructure feasibility of a double-blinded, placebo controlled RCT. The results of this pilot study will be used to investigate the feasibility of a formal larger RCT aiming to assess efficacy of perioperative propranolol to reduce PCa recurrence and progression after RALP.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 40 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →Oslo University Hospital is the lead sponsor of 810 studies on the registry; 148 are open to participants now.
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Exclusion Criteria:
Medical Conditions
Participants with known substance- or alcohol-abuse
Prior/Concomitant Therapy
Recommendations in the Summary of Product Characteristics for propranolol regarding concomitant use of other medications will be adhered to.
Diagnostic assessments
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
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
Also known as: Pranolol
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.
Time frame: The total duration of study participation from screening to end of follow-up is 50-102 days per participant. The primary outcome will be assessed when inclusion is completed, or if inclusion is not completed within 12 months.
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.
Time frame: 9 weeks
Determine the effect of RALP on catecholamine levels
Changes in catecholamine levels in the perioperative period.
Time frame: Up to 5 weeks
Determine the bioavailability of propranolol
Serum levels of propranolol pre-operatively and at end of PeP-RALP medication.
Time frame: Up to 5 weeks
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.
Time frame: 7-14 days
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.
Time frame: Up to 9 weeks
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).
Time frame: 1 day
Surgical complications
Frequence (n=) and severity of surgical complications as classified by the Clavian-Dindo classification.
Time frame: Up to 9 weeks
Change in perceived distress during the study.
Investigate alterations in perioperative perceived distress, assessed by Hospital Anxiety and Depression Scale (HADS)
Time frame: Up to 9 weeks
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.
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
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)
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
Differences between intervention arms with regard to intraoperative alterations in cerebral autoregulation and intracranial pressure, measured by transcranial doppler (TCD) floe velocity.
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
Plan to share: No — IPD that underlie the results reported in a published articles based on this study, after deidentification (text, tables, figures, and appendices)
This study is completed, as verified in May 2024. You cannot join it, but the record below documents what was studied.
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Oslo University Hospital