MELABLOCK: A Clinical Trial on the Efficacy and Safety of Propranolol 80 mg in Melanoma Patients

NCT02962947 | Unknown Phase 2

• 1 other identifier: EudraCT 2014---003970---18
• Study Type: interventional
• Target: 546
• Locations: 0 countries
• Sites: N/A

Brief Summary

The effectiveness of propranolol in infantile hemangiomas, the apparent better response to propranolol in breast cancer and the use of propranolol in a proportion of patients who did not develop melanoma recurrence suggested to use this unselective β---blocker to test the study hypothesis. The investigators propose a randomized double---blind placebo---controlled clinical trial (RTC) to evaluate whether the treatment with propranolol 80 mgR/die reduce the risk of CMM recurrence and mortality. Patients with resected stage II/IIIA CMM will be recruited in various Centers in Italy. Participants will be randomly assigned to propranolol treatment or placebo (1:1 ratio), treated for at least 1 year and followed for 2 years. Recruitment will proceed simultaneously at the different Centers, and will be completed in 2 years. The primary outcome of the entire trial will be, however, estimated by assessing a reduction in overall mortality at five years. The investigators will also evaluate general CMM recurrence and CMM specific mortality.

Conditions

Melanoma

Keywords

Melanoma; Propanolol; Betablockers

Outcome Measures

Primary Outcomes (1)

• Effect of Propranolol on overall survival for melanoma patients in stage II/IIIA (T2, N0 or N1, M0)

  To assess the effect of treatment with propranolol 80 mg retard (R) on overall survival for cutaneous malignant melanoma (CMM) patients in stage II/IIIA (T2, N0 or N1, M0) at five years of follow---up,after at least one year of treatment. Chi-square and Fisher's exact tests will be used to analyze the associations between the categorical variables. Logistic regression adjusting for confounding factors will be also performed. Wilcoxon tests will be used to compare continuous variables. Overall survival and Disease Free Survival curves will be estimated by the Kaplan-Meier method. Log-rank test will be used to compare survival time between groups and Cox proportional hazards models to evaluate the effect of β-blockers treatment and duration of treatment on melanoma recurrence and mortality, considering stratification factors.

  5 years

Secondary Outcomes (3)

• Effect of Propranolol on disease free survival for melanoma patients in stage II/IIIA

  5 years

• Effect of propranolol on specific mortality for melanoma patients in stage II/IIIA

  5 years

• Effect of propranolol treatment on the long-term safety on melanoma patients in stage II/IIIA

  5 years

Study Arms (2)

PLACEBO

PLACEBO COMPARATOR

Placebo will be taken daily during the study period

Drug: Placebo

PROPRANOLOL

ACTIVE COMPARATOR

Study participants in the treated group will take 80 mgR propranolol once daily .

Drug: Propranolol

Interventions

Propranolol DRUG

80 mgR propranolol once daily

PROPRANOLOL

Placebo DRUG

placebo once daily

PLACEBO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage: Ib (T1b, T2a), IIa (T2b, T3a), IIb (T3b T4a) and IIc (T4b), N0, M0; IIIA (N1a, N1b)
• Signed Informed Consent;
• Performance Status of 0---1 (ECOG);
• Hematopoietic functionality at the entry of the study: leukocytes, platelets, hemoglobin and neutrophils within the normal limits of laboratory references;
• Hepatic and renal functionality at the entry of the study: LDH, bilirubin, AST, ALT, alkalinephosphatase, BUN and serum creatinine within the normal range of each laboratory;

You may not qualify if:

• Primary not cutaneous melanoma;
• Clinical/radiological evidence or laboratory/pathology report of not completely resectedmelanoma;
• History of cancer
• Current use or past use in the last two years of any b---blockers for any other medical condition
• Current use of verapamil, diltiazem or similar calcium channel blocker
• Current use of centrally acting antihypertensive drugs as α---methyldopa, clonidine
• Hypersensitivity to propranolol or to any of the excipients;
• Acute heart failure or during episodes of heart failure decompensation requiring i.v.
• inotropic therapy;
• Cardiogenic shock;
• Sinoatrial block ;
• Second or third degree atrio---ventricular block;
• Marked bradycardia (less than 60 beats/min) ;
• Extreme hypotension (systolic blood pressure \<100mmHg) ;
• Severe asthma or severe chronic obstructive pulmonary disease ;

Sponsors & Collaborators

• Azienda Sanitaria di Firenze: lead

Related Publications (17)

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  PMID: 20091622 BACKGROUND

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  PMID: 17433471 BACKGROUND

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  PMID: 24182700 BACKGROUND

• 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

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  PMID: 20732454 BACKGROUND

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  PMID: 18550886 BACKGROUND

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MeSH Terms

Conditions

Melanoma

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

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

VINCENZO DE GIORGI, MD

CONTACT

+393356249012; vincenzo.degiorgi@unifi.it

Study Design

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

Study Record Dates

• First Submitted: February 19, 2016
• First Posted: November 15, 2016
• Study Start: June 1, 2017
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2022
• Last Updated: November 15, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share