Efficacy of Propranolol Treatment to Prevent Melanoma Progression

NCT01988831 | Suspended Phase 2

• 1 other identifier: HUG-MEL-BB
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stages III Skin Melanoma; Stages II Skin Melanoma; Stage IB Skin Melanoma

Keywords

Malignant melanoma; betablocker; propranolol; interventional; prospective; adjuvant; recurrence

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Use of serum microRNA profile as a predictor for recurrence

  5 years

• Overall survival

  5 years

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Betablocker

EXPERIMENTAL

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

Interventions

Propranolol hydrochloride DRUG

This intervention apply to Propranolol group

Also known as: Inderal, Avlocardyl, Hemipralon LP, Propranolol EG, PROPRANOLOL Ratiopharm, Propranolol Teva

Betablocker

Placebo pill DRUG

We use placebo pills alike propranolol commercial pills to ensure blindness of the subjects during the study.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

Hôpital universitaire de Genève

Geneva, Canton of Geneva, 1211, Switzerland

Location

Related Publications (3)

• De Giorgi V, Grazzini M, Gandini S, Benemei S, Lotti T, Marchionni N, Geppetti P. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med. 2011 Apr 25;171(8):779-81. doi: 10.1001/archinternmed.2011.131.

  PMID: 21518948 BACKGROUND

• Lemeshow S, Sorensen HT, Phillips G, Yang EV, Antonsen S, Riis AH, Lesinski GB, Jackson R, Glaser R. beta-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev. 2011 Oct;20(10):2273-9. doi: 10.1158/1055-9965.EPI-11-0249. Epub 2011 Sep 20.

  PMID: 21933972 BACKGROUND

• De Giorgi V, Gandini S, Grazzini M, Benemei S, Marchionni N, Geppetti P. Effect of beta-blockers and other antihypertensive drugs on the risk of melanoma recurrence and death. Mayo Clin Proc. 2013 Nov;88(11):1196-203. doi: 10.1016/j.mayocp.2013.09.001.

  PMID: 24182700 BACKGROUND

MeSH Terms

Conditions

Melanoma; Recurrence

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Frédérique-Anne Le Gal, MD/PhD

  Hôpital cantonal universitaire de Genève

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician, PD, MD/PhD

Study Record Dates

• First Submitted: November 13, 2013
• First Posted: November 20, 2013
• Study Start: June 1, 2016
• Primary Completion: January 1, 2022
• Study Completion: March 1, 2022
• Last Updated: May 10, 2019

Record last verified: 2019-05

Locations

CH (1)