Clinical Trials Register

Summary
EudraCT Number:	2017-003653-42
Sponsor's Protocol Code Number:	CRO-2017-34
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-09-07
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2017-003653-42

A.3

Full title of the trial

Phase II study to assess efficacy and safety of metronomic oral Idarubicin in patients with hepatocarcinoma at intermediate-advanced stage after failure or intolerance to Sorafenib and Regorafenib

Studio di Fase II che valuta l’efficacia e la sicurezza del trattamento metronomico orale con Idarubicina in pazienti affetti da Epatocarcinoma allo stadio intermedio-avanzato dopo fallimento o intolleranza a Sorafenib e Regorafenib

A.3.1

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

Study to assess efficacy and safety of the medication named Idarubicin given orally every other day to patients with advanced tumor of the liver who progressed or are intoelrant to the medication Sorafenib and Regorafenib

Studio che valuta l’efficacia e la sicurezza del farmaco Idarubicina dato oralmente a giorni alterni in pazienti affetti da tumore del fegato avanzato che non rispondono più al trattamento o hanno presentato intolleranza al farmaco Sorafenib e Regorafenib

A.3.2

Name or abbreviated title of the trial where available

Metro IDA

A.4.1

Sponsor's protocol code number

CRO-2017-34

A.5.4

Other Identifiers

Name:

n.a.

Number:

n.a.

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	CENTRO DI RIFERIMENTO ONCOLOGICO
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	CRO Aviano IRCCS
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	Centro di Riferimento Oncologico (CRO) - IRCCS Aviano
B.5.2	Functional name of contact point	S.O.C. Farmacologia Sperimentale e
B.5.3	Address:
B.5.3.1	Street Address	Via Franco Gallini, 2
B.5.3.2	Town/ city	Aviano
B.5.3.3	Post code	33081
B.5.3.4	Country	Italy
B.5.4	Telephone number	0434 659612
B.5.5	Fax number	0434 659799
B.5.6	E-mail	dirscienti@cro.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	ZAVEDOS - 5 MG CAPSULE RIGIDE FLACONE DA 1 CAPSULA
D.2.1.1.2	Name of the Marketing Authorisation holder	PFIZER ITALIA S.R.L.
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.3.1	Product name	Zavedos
D.3.2	Product code	027441031
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with interemdiate-advanced stage hepatocarcinoma

Pazienti affetti da epatocarcinoma allo stadio intermedio-avanzato

E.1.1.1

Medical condition in easily understood language

Patients with tumor of the liver

Pazienti affetti da tumore del fegato

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10024662
E.1.2	Term	Liver cell carcinoma non-resectable
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

6 month overall survival evaluation in patients with intermediate-advanced hepatic carcinoma treated with metronomic IDA

Valutazione dell’ overall survival (OS) a 6 mesi in pazienti affetti da CEC intermedio o avanzato trattati con IDA metronomica

E.2.2

Secondary objectives of the trial

- Evaluation of progression free survival (PFS) and time to progression (TTP)
- Evaluation of safety and tolerability of Idarubicin
- Evaluation of the impact of metronomic treatment with IDA on quality of life

- Valutazione della progressione free survival (PFS) e del time to progression (TTP)
- Valutazione del profilo di sicurezza e tollerabilità del farmaco
- Valutare l’impatto sulla qualità della vita del trattamento metronomico con IDA

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients with
- Advanced hepatocarcinoma (BCLC-C) progressed or intolerant to Sorafenib, or when Sorafenib and Regorafenib is controindicated, or
- intermediate hepatocarcinoma (BCLC-B) not suitable or not responsive to chemoembolization (TACE), who progressed or are intolerant to Sorafenib and Regorafenib or when Sorafenib and Regorafenib is controindicated
• A-B7 Child-Pugh score
• Measurable or evaluable disease according to RECIST v1.1 criteria
• Age >/= 18.
• ECOG PS = 0-1
• Adequate bone marrow, liver and renal functions

• Pazienti affetti da:
- Epatocarcinoma allo stadio avanzato (BCLC-C) che sono in progressione o hanno sviluppato intolleranza a Sorafenib e Regorafenib o nei quali tale trattamento risulta controindicato, oppure
- Epatocarcinoma allo stadio intermedio (BCLC-B) non candidabili o non responsivi a chemioembolizzazione (TACE) e che sono in progressione o hanno sviluppato intolleranza a Sorafenib e Regorafenib o nei quali tali trattamenti risultino controindicati
• Child-Pugh score A-B7
• Malattia misurabile o valutabile secondo criteri RECIST v1.1
• Età >/= 18.
• ECOG PS pari a 0-1
• Adeguata funzionalità midollare, epatica e renale

E.4

Principal exclusion criteria

• Previous treatment with molecular target therapy with the exception of sorafenib.
• Life expectancy < 2 months
• clinically significant cardiovascular or cerebrovascular disease
• clinically significant acute or chronic respiratory failure
• History of previous tumors with DFS < 5 yrs with the exception of basocellular or spinocellular skin carcinoma, in situ carcinoma of the cervix, breast or bladder
• grade = 1 according to CTCAE residual toxicity from previous treatment .
• previous cumulative dose of 300 mg/m2 of doxorubicina or equivalent drug
• patients who are candidates to second line therapy with Regorafenib

• Precedente trattamento sistemico con terapie a bersaglio molecolare eccetto sorafenib.
• Pazienti con aspettativa di vita inferiore a due mesi
• Presenza di malattia cardiovascolare o cerebrovascolare clinicamente significativa
• Insufficienza respiratoria acuta o cronica clinicamente significativa
• Anamnesi di altra neoplasia maligna con un intervallo libero da malattia inferiore a 5 anni dall’arruolamento, con eccezione per il carcinoma a cellule o basali e squamoso della cute, e per il carcinoma in situ della cervice, della mammella, o della vescica.
• Presenza di tossicità residua da precedenti trattamenti sintomatica di grado = 1 secondo CTCAE.
• Precedente dose cumulativa di 300 mg/m2 di doxorubicina o equivalenti.
• pazienti che sono candidati ad una terapia di seconda linea con Regorafenib

E.5 End points

E.5.1

Primary end point(s)

6 month-overall survival

Overall survival a 6 mesi

E.5.1.1

Timepoint(s) of evaluation of this end point

2 years

2 anni

E.5.2

Secondary end point(s)

Evaluation of progression free survival and time to progression; Evaluate the possible correlation between IDA and IDOLO Ctrough levels and haematologic toxicity (G>2) and response.; Evaluate proteomic and metabolomic biomarkers in patients treated with Idarubicin; Evaluate the effect of "immunogenic cell death"

Valutazione della progression free survival e del time to progression; Studiare l’eventuale correlazione tra livelli di Ctrough di IDA e IDOLO e tossicità ematologica (G>2) e la possibile correlazione tra Ctrough e risposta.; Valutare i parametri proteomici e metabolomici, in ogni paziente arruolato nello studio valutando il potenziale potere sia del farmaco (IDA) che del suo metabolita (IDOLO) nella determinazione di sottogruppi miglior rispondenti. Sarà quindi eseguita una correlazione con i principali parametri farmacocinetici. ; Valutare l'effetto di "immunogenic cell death"

E.5.2.1

Timepoint(s) of evaluation of this end point

2 years; 2 years; 2 years; 2 years

2 anni; 2 anni; 2 anni; 2 anni

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

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

LVLS

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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)

Follow up

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

2018-10-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-11-20

P. End of Trial
P.	End of Trial Status	Prematurely Ended

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials