Clinical Trials Register

Summary
EudraCT Number:	2014-003970-18
Sponsor's Protocol Code Number:	MELABLOCK
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-09
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-003970-18

A.3

Full title of the trial

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

studio clinico multicentrico, randomizzato, controllato, con placebo, in doppio cieco per valutare l'efficacia e la sicurezza di propranololo 80 mg retard per la prevenzione dl ricorrenze di melanoma maligno

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

clinical trial to assess efficacy and safety of once daily 80 mg propranolol therapy to overall survival for cutaneous melanoma

studio sperimentale per verificare l'efficacia e la sicurezza della terapia con propranololo 80 mg una volta al giorno nel migliorare il decorso del melanoma cutaneo

A.3.2

Name or abbreviated title of the trial where available

MELABLOCK

A.4.1

Sponsor's protocol code number

MELABLOCK

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZIENDA SANITARIA DI FIRENZE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Istituto Toscano Tumori
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	azienda sanitaria firenze
B.5.2	Functional name of contact point	struttura coordinamento ricerca cli
B.5.3	Address:
B.5.3.1	Street Address	p.o. palagi-viale michelangiolo 41
B.5.3.2	Town/ city	firenze
B.5.3.3	Post code	50135
B.5.3.4	Country	Italy
B.5.4	Telephone number	0556937574
B.5.5	Fax number	0556937357
B.5.6	E-mail	elisa.danti@asf.toscana.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	INDERAL - 80 MG CAPSULE RIGIDE A RILASCIO PROLUNGATO 28 CAPSULE
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Prolonged-release tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PROPRANOLOLO
D.3.9.2	Current sponsor code	SIS:2638
D.3.9.3	Other descriptive name	beta blocker
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

melanoma

E.1.1.1

Medical condition in easily understood language

tumore cutaneo

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10053571
E.1.2	Term	Melanoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

to assess the effect of treatment with propanololo 80 mg retard on overall survival for melanoma patients in stage II/IIIA (T2, N0 or N1, M0) at 5 years follow-up after at least one years of treatment

valutare l'efficacia del trattamento con propanololo 80 mg R sulla sopravvivenza globale per pazienti affetti da melanoma in stadio II/IIA (T2, N0 or N1, M0) dopo 5 anni di follow-up e almeno un anno di trattamento

E.2.2

Secondary objectives of the trial

to evaluate the effect of treatment on disease free survival at five years follow-up in patinets stage II/IIA
to evaluate the effect of treatment of specific mortality for melanoma
to evaluate the long term safaty of treatment in patient with melanoma stage II/IIIA
to evaluate the adherence to propanololo treatment (compliance)

valutazione del periodo libero da malattia a 5 anni per melanoma in stadio II/IIIA trattati con propanololo;
valutare l'effetto del trattamento sulla mortalità specifica per melanoma nei pazienti trattati;
valutare la sicurezza a lungo termine del trattamento nei pazienti con melanoma stadio II/IIIA;
valutare l'aderenza alla terapia (compliace) del trattamento con propanololo nei pazienti affetti da melanoma

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 18-75 years old with newly diagnosed histologically proven resected melanoma;
2. Stage: Ib (T1b, T2a), IIa (T2b, T3a), IIb (T3b T4a) and IIc (T4b), N0, M0; IIIA (N1a, N1b)
3. Signed Informed Consent;
4. Performance Status of 0-1 (ECOG);
5. Hematopoietic functionality at the entry of the study: leukocytes, platelets, hemoglobin and neutrophils within the normal limits of laboratory references;
6. 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;

18-75 anni di età; firma del consenso informato, status ECOG 0-1; funzionalità epatica e renale nei limiti; Stage: Ib (T1b, T2a), IIa (T2b, T3a), IIb (T3b T4a) and IIc (T4b), N0, M0; IIIA (N1a, N1b)

E.4

Principal 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 a-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;
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 breast feeding.

tumori precedenti, presenza di metastasi, uso di beta-bloccanti in passato per altra causa, assunzione di verapamil, diltiazem o similari, uso di antidepressivi come l'alpha metiildopa, ipersensività al propanololo, infarto, shock cardiogeno, blocco del nodo senoatriale, bradicardia marcata, ipotensione sistolica (<100 mmHg), asma, acidosi metabolica, diabete, storia di psoriasi, gravidanza, allattamento,

E.5 End points

E.5.1

Primary end point(s)

ndn

sopravvivenza, periodo libero da malattia

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

Overall survival (OS) will be the primary end-point of efficacy in this Phase III trial. It is defined as the time from the date of randomization to the date of death from any cause or to the date of last follow-up. Every effort should be made to document the latest date of follow-up/date of death and the cause of death. Patients still alive at the latest follow-up will be considered as censored observations.; We will include in this study histologically confirmed CMM diagnosed before their recruitment (date at interview) in the trial and before the end of the last follow-up period. We will evaluate progression or death before the end of the last follow-up period.

Sopravvivenza globale; Sopravvivenza libera da malattia

E.5.2.1

Timepoint(s) of evaluation of this end point

5 years; 5 years

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

Yes

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

n.a.

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

n.a.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-08

P. End of Trial
P.	End of Trial Status	Ongoing

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