Efficacy of Propranolol Treatment to Prevent Melanoma Progression

Study Overview
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Brief Summary
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Melanoma's incidence is increasing worldwide. The efforts made in melanoma screening led to an earlier detection of the primary tumour and a better prognosis, but melanoma remains an aggressive cancer when it comes to its metastatic stage. Three recent retrospective studies compared groups of patients diagnosed with primary melanoma and treated with betablockers for another indication to patients who never received betablockers. In these three studies, the outcome of the disease is significantly better for people under betablocker treatment with a decreased rate of recurrence and a better 5 years survival rate. Here we want to investigate the efficacy and the tolerability of an adjuvant treatment with propranolol for patients suffering from a primary melanoma with a high risk of recurrence.

Official Title
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Phase 2 Prospective Study of the Efficacy of Propranolol on Malignant Melanoma Progression. A Randomized Placebo-controlled,Single Blind Trial

Conditions
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Stages III Skin Melanoma, Stages II Skin Melanoma, Stage IB Skin Melanoma

Intervention / Treatment
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* Drug: Propranolol hydrochloride
* Drug: Placebo pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patient over 18 y.o Breslow index > 1mm or any Breslow index with ulcerated primary lesion Melanoma stage AJCC Ib, IIa, IIb, IIc, IIIa, IIIb or IIIc Able to undergo outpatient treatment Exclusion Criteria: No contra indication for betablockers as defined by the compendium No clinical evidence of coagulopathy No unstable angina pectoris No AV-block II or III without pacemaker No severe congestive heart failure No untreated phaeochromocytoma No severe bradycardia No severe hypotension No severe impairment of peripheral arterial circulation No uncontrolled cardiac arrhythmia No severe asthma or COPD No uncontrolled diabetes mellitus No Angioneurotic edema No severe Aortic valve stenosis No severe hypertrophic cardiomyopathy No severe renal dysfunction No patients on beta blockers by inclusion No known adverse reaction to betablockers No pregnant or lactating patients can be included No melanoma stage AJCC IV by inclusion No patients requiring a specific oncological treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>113 patients will be enrolled in the placebo group with respect to randomization. Placebo group will be prescribed placebo pills in the same packaging as propranolol treated group. The frequency and duration of the treatment is the same as propranolol arm. The placebo group will have the same cardiology consultation as propranolol treated group to ensure the respect of blindness. | Drug: Placebo pill<br>* We use placebo pills alike propranolol commercial pills to ensure blindness of the subjects during the study.<br>|
| Experimental: Betablocker<br>drug: 'Propranolol hydrochloride' 338 patients will be enrolled in the Propranolol Group and treated with propranolol. The dosage will be determined by the cardiologist as the maximum tolerated dose to a maximum of 160mg/day. One long acting pill a day until an evidence of disease progression or the end of the study. | Drug: Propranolol hydrochloride<br>* This intervention apply to Propranolol group<br>* Other names: Propranolol Teva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of propranolol on progression free survival for patients suffering from a primary melanoma with a high risk of recurrence | The efficacy of propranolol treatment will be tested in one interim analysis when the last patient enrolled have reached one year of follow up and one final analysis when the last patient enrolled have reached three years of follow up. The primary endpoint of the study will be the progression of the disease. We will measure the efficacy of a propranolol treatment on the risk of progression of the disease. | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Use of serum microRNA profile as a predictor for recurrence | We will investigate the microRNA profile in the serum of patients of both groups during the whole study to identify biomarkers specific for recurrence. | 5 years | 
| Overall survival | We investigate the impact of propranolol treatment on the 5 years survival. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant melanoma, betablocker, propranolol, interventional, prospective, adjuvant, recurrence