E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this pilot is to establish the recruitment- and infrastructure- feasibility of a double-blinded, placebo controlled RCT of perioperative propranolol in patients undergoing RALP. The results of this pilot study is to be the foundation for a formal larger RCT with the aim to assess efficacy of perioperative propranolol to reduce PCa recurrence and progression after RALP. Adverse effects (AEs) and serious adverse effects (SAEs) to the drug will be analyzed throughout the study. |
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E.2.2 | Secondary objectives of the trial |
1-Safety and tolerability of PeP-RALP intervention 2-Determine the effect of RALP on catecholamine levels 3-Determine the bioavailability of propranolol 4-Determine the effect of preoperative propranolol treatment on the serum level of PSA 5-To determine the effect of propranolol on post-operative biochemical failure 6-Surgical complications in PeP RALP patients 7-Intraoperative challenges
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent. 2. Participants with prostate cancer stratified into European Association of Urology intermadiate-risk and high-risk for biochemical recurrence planned for curative robotic assisted laparoscopic prostatectomy 3. Participants who are in the ECOG PS 0-1 as determined by medical evaluation including medical history, physical examination, laboratory tests, electrocardiogram (ECG). 4. Willing to-, and capable of, giving signed informed consent in Norwegian which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
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E.4 | Principal exclusion criteria |
Medical Conditions 1. Sick sinus syndrome 2. Atrioventricular (AV) block grade 2 and 3 3. Recent (3 months) myocardial infarction 4. Known unstable- or vasospastic- angina 5. Heart failure (New York Heart Association [NYHA] > 2) 6. Symptomatic peripheral vascular disease (e.g. intermittent claudication) 7. Known pulmonary hypertension 8. Known carotid artery stenosis or recent (3 months) stroke 9. Bronchial asthma or other chronic obstructive pulmonary disease (COPD) 10. Kidney failure (estimated Glomerular filtration rate [eGFR]<50) 11. Liver failure (cirrhosis, jaundice, signs of hepatic decompression) 12. Unregulated diabetes mellitus 13. Untreated thyroid disorder 14. Depressive episode within last 6 months (within last 12 months if major depressive episode) 15. Known drug allergy against propranolol or excipients 16. Any medical conditions considered to prohibit Propranolol use as judged by the treating physician (including frailty). 17. Participants with known substance- or alcohol-abuse Prior/Concomitant Therapy 18. Recent (<3 month) use of systemic beta-blockers prior to screening. 19. Patients receiving non-dihydropyridine calcium channel blocking agents (eg diltiazem, verapamil) 20. Patients receiving anti-arrhythmic agents (e.g. amiodarone, sotalol, digoxin, verapamil, flecainide) 21. Patients receiving digoxin, rizatriptan, hydralazine, fluvoksamin, or fluoksetin 22. Patients using daily anxiolytics (e.g. benzodiazepines), alpha-receptor adrenergic agonists (e.g. clonidine)
Diagnostic assessments 23. Sinus bradycardia (<60 beats/minute) 24. Resting blood pressure <110/60mmHg OR hypertension BP >160/100 25. AV-block on ECG
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E.5 End points |
E.5.1 | Primary end point(s) |
Numbers needed to screen
Compliance before RALP >80% Compliance after RALP > 80%
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
to be evaluated at end of study |
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E.5.2 | Secondary end point(s) |
1: Proportion of patients experiencing treatment related clinical significant hypotension and/or bradycardia. Adverse events of PeP-RALP medication. Proportion of patients tolerating daily dose of 80mg propranolol. 2: Changes in catecholamine levels in the perioperative period. 3: Serum levels of propranolol pre-operatively and at end of PeP-RALP medication. 4: Changes in PSA levels after 7-14 days of PeP-RALP medication. 5: Proportion of patients with serum PSA levels above 0.1 ng/ml at 6 weeks post-RALP. 6: Frequency and severity of surgical complications 7: Anesthesiological challenges. Surgical challenges.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Adverse events are to be assessed continuously until follow up.
All other end points are to be evaluated at end of study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
This is a feasability study. We do not aim to have the statistical power to show efficacy, but this will however be assessed, by means of surrogate markers of recurrence, and reported descriptively. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |