Ignite Creation Date:
2025-12-25 @ 1:21 AM
Ignite Modification Date:
2025-12-25 @ 11:29 PM
Study NCT ID:
NCT05679193
Status:
COMPLETED
Last Update Posted:
2024-05-29
First Post:
2022-12-12
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D011471', 'term': 'Prostatic Neoplasms'}], 'ancestors': [{'id': 'D005834', 'term': 'Genital Neoplasms, Male'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D005832', 'term': 'Genital Diseases, Male'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D011469', 'term': 'Prostatic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D011433', 'term': 'Propranolol'}], 'ancestors': [{'id': 'D050198', 'term': 'Phenoxypropanolamines'}, {'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'parallel-group, phase 2, double-blind, 2-arm study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 40}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2023-01-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-05', 'completionDateStruct': {'date': '2024-01-27', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-05-27', 'studyFirstSubmitDate': '2022-12-12', 'studyFirstSubmitQcDate': '2023-01-09', 'lastUpdatePostDateStruct': {'date': '2024-05-29', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-01-10', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-11-28', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Change in perceived distress during the study.', 'timeFrame': 'Up to 9 weeks', 'description': 'Investigate alterations in perioperative perceived distress, assessed by Hospital Anxiety and Depression Scale (HADS)'}, {'measure': '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.', 'timeFrame': 'Up to 9 weeks', 'description': 'Immunohistochemistry and image mass cytometry to assess for differences between treatment arms in intra-tumor immune cell infiltration.\n\nFlow cytometry to assess differences between treament arms in systemic immune cell acitivity.'}, {'measure': '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)', 'timeFrame': 'up to 1 year', 'description': 'Determine the effect of pre-operative propranolol treatment on prognostic markers and assess for predictive biomarkers. Identify predictive biomarkers for propranolol responsiveness.'}, {'measure': 'Differences between intervention arms with regard to intraoperative alterations in cerebral autoregulation and intracranial pressure, measured by transcranial doppler (TCD) floe velocity.', 'timeFrame': 'up to 1 year', 'description': 'Intraoperative alterations in cerebral autoregulation and intracranial pressure by Transcranial Doppler flow velocity measurement of the middle cerebral artery.'}], 'primaryOutcomes': [{'measure': 'The feasibility of conducting a formal larger RCT to compare the efficacy of propranolol vs placebo to decrease PCa recurrence following RALP.', 'timeFrame': '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.', '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.\n\nCompliance 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.'}], 'secondaryOutcomes': [{'measure': 'Safety and tolerability of PeP-RALP intervention', 'timeFrame': '9 weeks', 'description': 'Safety:\n\nProportion (%) of patients experiencing treatment related clinical significant hypotension and/or bradycardia.\n\nAdverse events of PeP-RALP medication as assessed by CTCAE v5.0.\n\nTolerability:\n\nProportion (%) of patients tolerating daily dose of 80mg propranolol.'}, {'measure': 'Determine the effect of RALP on catecholamine levels', 'timeFrame': 'Up to 5 weeks', 'description': 'Changes in catecholamine levels in the perioperative period.'}, {'measure': 'Determine the bioavailability of propranolol', 'timeFrame': 'Up to 5 weeks', 'description': 'Serum levels of propranolol pre-operatively and at end of PeP-RALP medication.'}, {'measure': 'Determine the effect of preoperative propranolol treatment on the serum level of PSA', 'timeFrame': '7-14 days', 'description': 'Changes in PSA levels after 7-14 days of PeP-RALP medication.'}, {'measure': 'To determine the effect of propranolol on post-operative biochemical failure', 'timeFrame': 'Up to 9 weeks', 'description': 'Proportion of patients with serum PSA levels above 0.1 ng/ml at 6 weeks post-RALP.'}, {'measure': 'Intraoperative anesthesiological and surgical challenges Surgical complications in PeP RALP patients', 'timeFrame': '1 day', 'description': 'Anesthesiological challenges are assed by:\n\nProportion of patients (%) in each intervention group requiring vasopressors to maintain an acceptable mean arterial pressure (MAP \\>60mmhg). Amount of vasopressor needed.\n\nSurgical challenges are assed by:\n\nThe surgical procedure time (minutes) and estimated intraoperative blood loss (milliliters).'}, {'measure': 'Surgical complications', 'timeFrame': 'Up to 9 weeks', 'description': 'Frequence (n=) and severity of surgical complications as classified by the Clavian-Dindo classification.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Prostate Cancer']}, 'referencesModule': {'references': [{'pmid': '35080602', 'type': 'BACKGROUND', 'citation': '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': '26969754', 'type': 'BACKGROUND', 'citation': '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': '31754048', 'type': 'BACKGROUND', 'citation': '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': '28490464', 'type': 'BACKGROUND', 'citation': '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': '29800703', 'type': 'BACKGROUND', 'citation': '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': '28344958', 'type': 'BACKGROUND', 'citation': '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': '32533792', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.\n\nThe 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.\n\nPerioperative 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.\n\nOur 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}.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '40 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* European Association of Urology Intermediate- and High Risk for Biochemical recurrence and planned for curative RALP\n* ECOG Performance Status 0-1\n\nExclusion Criteria:\n\nMedical Conditions\n\n1. Sick sinus syndrome\n2. Atrioventricular (AV) block grade 2 and 3\n3. Recent (3 months) myocardial infarction\n4. Known unstable- or vasospastic- angina\n5. Heart failure (New York Heart Association \\[NYHA\\] \\> 2)\n6. Symptomatic peripheral vascular disease (e.g. intermittent claudication)\n7. Known pulmonary hypertension\n8. Known carotid artery stenosis or recent (3 months) stroke\n9. Bronchial asthma or other chronic obstructive pulmonary disease (COPD)\n10. Kidney failure (estimated Glomerular filtration rate \\[eGFR\\]\\<50)\n11. Liver failure (cirrhosis, jaundice, signs of hepatic decompression)\n12. Unregulated diabetes mellitus\n13. Untreated thyroid disorder\n14. Depressive episode within last 6 months (within last 12 months if major depressive episode)\n15. Known drug allergy against propranolol or excipients\n16. Any medical conditions considered to prohibit Propranolol use as judged by the treating physician (including frailty).\n17. Participants with known substance- or alcohol-abuse\n\n Prior/Concomitant Therapy\n18. Recent (\\<3 month) use of systemic beta-blockers prior to screening.\n19. Patients receiving non-dihydropyridine calcium channel blocking agents (eg diltiazem, verapamil)\n20. Patients receiving anti-arrhythmic agents (e.g. amiodarone, sotalol, digoxin, verapamil, flecainide)\n21. Patients receiving digoxin, rizatriptan, hydralazine, fluvoksamin, or fluoksetin\n22. Patients using daily anxiolytics (e.g. benzodiazepines), alpha-receptor adrenergic agonists (e.g. clonidine)\n23. Recommendations in the Summary of Product Characteristics for propranolol regarding concomitant use of other medications will be adhered to.\n\n Diagnostic assessments\n24. Sinus bradycardia (\\<60 beats/minute)\n25. Resting blood pressure \\<110/60mmHg OR hypertension BP \\>160/100\n26. AV-block 2 or 3 on ECG'}, 'identificationModule': {'nctId': 'NCT05679193', 'acronym': 'PeP-RALP', 'briefTitle': 'Perioperative Propranolol During Prostatectomy to Decrease Cancer Recurrence', 'organization': {'class': 'OTHER', 'fullName': 'Oslo University Hospital'}, 'officialTitle': 'Perioperative Propranolol in Robotic Assisted Laparoscopic Prostatectomy- A Feasibility Study of Propranolol to Target Perioperative Stress Induced Cancer Progression', 'orgStudyIdInfo': {'id': '488466'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Propranolol', '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.', 'interventionNames': ['Drug: Propranolol']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', '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.', 'interventionNames': ['Drug: Propranolol']}], 'interventions': [{'name': 'Propranolol', 'type': 'DRUG', 'otherNames': ['Pranolol'], 'description': 'Propranolol capsules 20mg taken orally.\n\nDay: 1-3:\n\n20mg twice daily\n\nDay: 4-19 (25 , In cases of delayed RALP an extension of up to 6 days is allowed.in cases of delayed surgery).\n\n2x 20mg twice daily\n\nDay 20-22 20mg twice daily', 'armGroupLabels': ['Placebo', 'Propranolol']}]}, 'contactsLocationsModule': {'locations': [{'zip': '4953', 'city': 'Oslo', 'country': 'Norway', 'facility': 'Oslo University Hospital The Norwegian Radium Hospital', 'geoPoint': {'lat': 59.91273, 'lon': 10.74609}}], 'overallOfficials': [{'name': 'Shivanthe Sivanesan, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Oslo University Hospital'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'IPD that underlie the results reported in a published articles based on this study, after deidentification (text, tables, figures, and appendices)'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Oslo University Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'Ivar, Ragna og Morten Holes legat til fremme av kreftforskningen i Norge', 'class': 'UNKNOWN'}, {'name': 'Fondsstiftelsen ved Oslo Universitetssykehus', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Urologist and General Surgeon', 'investigatorFullName': 'Shivanthe Sivanesan', 'investigatorAffiliation': 'Oslo University Hospital'}}}}