Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence

NCT05679193 | Completed Phase 2

• 1 other identifier: 488466
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 (PCa) after robotic assisted laparoscopic prostatectomy (RALP) in participants with intermediate to high-risk for prostate cancer recurrence.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Secondary Outcomes (7)

• Safety and tolerability of PeP-RALP intervention

  9 weeks

• Determine the effect of RALP on catecholamine levels

  Up to 5 weeks

• Determine the bioavailability of propranolol

  Up to 5 weeks

• Determine the effect of preoperative propranolol treatment on the serum level of PSA

  7-14 days

• To determine the effect of propranolol on post-operative biochemical failure

  Up to 9 weeks

Other Outcomes (4)

• Change in perceived distress during the study.

  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.

  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)

  up to 1 year

Study Arms (2)

Propranolol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Propranolol DRUG

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

Placebo; Propranolol

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• European Association of Urology Intermediate- and High Risk for Biochemical recurrence and planned for curative RALP
• ECOG Performance Status 0-1

You may not qualify if:

• 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)

Sponsors & Collaborators

• Oslo University Hospital: lead
• Ivar, Ragna og Morten Holes legat til fremme av kreftforskningen i Norge: collaborator
• Fondsstiftelsen ved Oslo Universitetssykehus: collaborator

Study Sites (1)

Oslo University Hospital The Norwegian Radium Hospital

Oslo, 4953, Norway

Location

Related Publications (7)

• Sivanesan S, Tasken KA, Grytli HH. Association of beta-Blocker Use at Time of Radical Prostatectomy With Rate of Treatment for Prostate Cancer Recurrence. JAMA Netw Open. 2022 Jan 4;5(1):e2145230. doi: 10.1001/jamanetworkopen.2021.45230.

  PMID: 35080602 BACKGROUND

• Zhou L, Li Y, Li X, Chen G, Liang H, Wu Y, Tong J, Ouyang W. Propranolol Attenuates Surgical Stress-Induced Elevation of the Regulatory T Cell Response in Patients Undergoing Radical Mastectomy. J Immunol. 2016 Apr 15;196(8):3460-9. doi: 10.4049/jimmunol.1501677. Epub 2016 Mar 11.

  PMID: 26969754 BACKGROUND

• Hiller JG, Cole SW, Crone EM, Byrne DJ, Shackleford DM, Pang JB, Henderson MA, Nightingale SS, Ho KM, Myles PS, Fox S, Riedel B, Sloan EK. Preoperative beta-Blockade with Propranolol Reduces Biomarkers of Metastasis in Breast Cancer: A Phase II Randomized Trial. Clin Cancer Res. 2020 Apr 15;26(8):1803-1811. doi: 10.1158/1078-0432.CCR-19-2641. Epub 2019 Nov 21.

  PMID: 31754048 BACKGROUND

• Shaashua L, Shabat-Simon M, Haldar R, Matzner P, Zmora O, Shabtai M, Sharon E, Allweis T, Barshack I, Hayman L, Arevalo J, Ma J, Horowitz M, Cole S, Ben-Eliyahu S. Perioperative COX-2 and beta-Adrenergic Blockade Improves Metastatic Biomarkers in Breast Cancer Patients in a Phase-II Randomized Trial. Clin Cancer Res. 2017 Aug 15;23(16):4651-4661. doi: 10.1158/1078-0432.CCR-17-0152. Epub 2017 May 10.

  PMID: 28490464 BACKGROUND

• Haldar R, Shaashua L, Lavon H, Lyons YA, Zmora O, Sharon E, Birnbaum Y, Allweis T, Sood AK, Barshack I, Cole S, Ben-Eliyahu S. Perioperative inhibition of beta-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome. Brain Behav Immun. 2018 Oct;73:294-309. doi: 10.1016/j.bbi.2018.05.014. Epub 2018 May 22.

  PMID: 29800703 BACKGROUND

• Jang HI, Lim SH, Lee YY, Kim TJ, Choi CH, Lee JW, Kim BG, Bae DS. Perioperative administration of propranolol to women undergoing ovarian cancer surgery: A pilot study. Obstet Gynecol Sci. 2017 Mar;60(2):170-177. doi: 10.5468/ogs.2017.60.2.170. Epub 2017 Mar 16.

  PMID: 28344958 BACKGROUND

• Haldar R, Ricon-Becker I, Radin A, Gutman M, Cole SW, Zmora O, Ben-Eliyahu S. Perioperative COX2 and beta-adrenergic blockade improves biomarkers of tumor metastasis, immunity, and inflammation in colorectal cancer: A randomized controlled trial. Cancer. 2020 Sep 1;126(17):3991-4001. doi: 10.1002/cncr.32950. Epub 2020 Jun 13.

  PMID: 32533792 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Shivanthe Sivanesan, MD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Urologist and General Surgeon

Model Details: parallel-group, phase 2, double-blind, 2-arm study

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 10, 2023
• Study Start: January 2, 2023
• Primary Completion: November 28, 2023
• Study Completion: January 27, 2024
• Last Updated: May 29, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)