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

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ClinicalTrials.gov Identifier: NCT02962947
Recruitment Status : Not yet recruiting
First Posted : November 15, 2016
Last Update Posted : November 15, 2016
Sponsor:
Information provided by (Responsible Party):
VINCENZO DE GIORGI, MD, Azienda Sanitaria di Firenze

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Propranolol Drug: Placebo Phase 2 Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 546 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Melablock: A Multicentre Randomized, Double---blinded and Placebo---controlled Clinical Trial on the Efficacy and Safety of Once Daily Propranolol 80 mg Retard for the Prevention of Cutaneous Malignant Melanoma Recurrence
Study Start Date : June 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Placebo Comparator: PLACEBO
Placebo will be taken daily during the study period
Drug: Placebo
placebo once daily
Active Comparator: PROPRANOLOL
Study participants in the treated group will take 80 mgR propranolol once daily .
Drug: Propranolol
80 mgR propranolol once daily



Primary Outcome Measures :
  1. Effect of Propranolol on overall survival for melanoma patients in stage II/IIIA (T2, N0 or N1, M0) [ Time Frame: 5 years ]
    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.


Secondary Outcome Measures :
  1. Effect of Propranolol on disease free survival for melanoma patients in stage II/IIIA [ Time Frame: 5 years ]
    To evaluate the effect of treatment on disease free survival (DFS) at five years for CMM patients in stage II/IIIA. 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.

  2. Effect of propranolol on specific mortality for melanoma patients in stage II/IIIA [ Time Frame: 5 years ]
    To evaluate the effect of treatment on specific mortality for CMM patients in stage II/IIIA. 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.

  3. Effect of propranolol treatment on the long-term safety on melanoma patients in stage II/IIIA [ Time Frame: 5 years ]
    To evaluate the long---term safety of treatment on CMM patients in stage II/IIIA.This study will use the NCI Common Terminology Criteria for Adverse events version 3.0, for toxicity and adverse event reporting. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. A copy of the CTCAE can be found at http://ctep.cancer.gov. AEs will be assessed according to the CTCAE grade associated with the AE term. AEs that do not have a corresponding CTCAE term will be assessed according to their impact on the participant's ability to perform daily activities



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Stage: Ib (T1b, T2a), IIa (T2b, T3a), IIb (T3b T4a) and IIc (T4b), N0, M0; IIIA (N1a, N1b)
  2. Signed Informed Consent;
  3. Performance Status of 0---1 (ECOG);
  4. Hematopoietic functionality at the entry of the study: leukocytes, platelets, hemoglobin and neutrophils within the normal limits of laboratory references;
  5. 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;

Exclusion Criteria:

  1. Primary not cutaneous melanoma;
  2. Clinical/radiological evidence or laboratory/pathology report of not completely resectedmelanoma;
  3. History of cancer
  4. Current use or past use in the last two years of any b---blockers for any other medical condition
  5. Current use of verapamil, diltiazem or similar calcium channel blocker
  6. Current use of centrally acting antihypertensive drugs as α---methyldopa, clonidine
  7. Hypersensitivity to propranolol or to any of the excipients;
  8. Acute heart failure or during episodes of heart failure decompensation requiring i.v.

    inotropic therapy;

  9. Cardiogenic shock;
  10. Sinoatrial block ;
  11. Second or third degree atrio---ventricular block;
  12. Marked bradycardia (less than 60 beats/min) ;
  13. Extreme hypotension (systolic blood pressure <100mmHg) ;
  14. Severe asthma or severe chronic obstructive pulmonary disease ;
  15. Sick sinus syndrome;
  16. Severe forms of peripheral arterial occlusive disease and Raynaud's syndrome;
  17. Metabolic acidosis
  18. Asthma
  19. Diabetes
  20. Heart failure
  21. History of psoriasis
  22. Pregnancy or breast feeding or planning on becoming pregnant during the 3 years of treatment (for major details see the Section "Pregnancy in the Study", below);
  23. Any medical condition that in the physician's opinion would potentially interfere with the patient ability to adhere to protocol and treatment;
  24. Any logistic condition that do not allow follow---up of the disease of the patient.
  25. Hypersensitivity to propranolol, child bearing or breastfeeding.
  26. Pheocromocytoma 27. Prinzmetal's Angina 28. Fasting -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02962947


Contacts
Contact: VINCENZO DE GIORGI, MD +393356249012 vincenzo.degiorgi@unifi.it

Sponsors and Collaborators
Azienda Sanitaria di Firenze

Publications:

Responsible Party: VINCENZO DE GIORGI, MD, MD, Azienda Sanitaria di Firenze
ClinicalTrials.gov Identifier: NCT02962947     History of Changes
Other Study ID Numbers: EudraCT 2014---003970---18
First Posted: November 15, 2016    Key Record Dates
Last Update Posted: November 15, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by VINCENZO DE GIORGI, MD, Azienda Sanitaria di Firenze:
Melanoma
Propanolol
Betablockers

Additional relevant MeSH terms:
Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents