Clinical Trials Register

Summary
EudraCT Number:	2012-000869-21
Sponsor's Protocol Code Number:	Ima-NF1-2012
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:	2012-03-08
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

2012-000869-21

A.3

Full title of the trial

Pilot study: Imatinib for the treatment of plexiform neurofibromas in NF1 patients.

Studio pilota sul trattamento con Imatinib di neurofibromi plessiformi in pazienti con neurofibromatosi di tipo I

A.3.1

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

Imatinib treatment as therapy of neurofibromas in patients with NF1

Terapia con Imatinib per la cura dei neurofibromi nelle persone affette da neurofibromatosi 1

A.3.2

Name or abbreviated title of the trial where available

Ima-NF1-2012

A.4.1

Sponsor's protocol code number

Ima-NF1-2012

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	ISTITUTO NEUROLOGICO "CARLO BESTA"
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	Ministero della Salute - Bando Malattie Rare 2008
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	Fondazione Irccs Istituto Neurologico Carlo Besta
B.5.2	Functional name of contact point	Servizio Ricerca e Sviluppo Clinico
B.5.3	Address:
B.5.3.1	Street Address	via Celoria 11
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20133
B.5.3.4	Country	Italy
B.5.4	Telephone number	0223942321
B.5.5	Fax number	0223943569
B.5.6	E-mail	crc@istituto-besta.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	GLIVEC*24CPS 100MG
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/01/061
D.3 Description of the IMP
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IMATINIB
D.3.9.1	CAS number	152459-95-5
D.3.9.2	Current sponsor code	NA
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB25387
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	100
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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 NF1 and plessiform neurofibromas

Soggetti con neurofibromi plessiformi affetti da neurofibromatosi di tipo 1

E.1.1.1

Medical condition in easily understood language

Patients with Neurofibromatosis 1 and neurofibromas

Soggetti con neurofibromi affetti da neurofibromatosi di tipo 1

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10029104
E.1.2	Term	Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary aim of this proposal is to verify modification in the rating neurological scale adopted and to estimate progression free survival (according to an automated volumetric MRI analysis) in patients with not total resectable, disabling or disfiguring plexiform fibromas (see inclusion criteria) expressing c-KIT and treated with Imatinib mesylate.

Primario: determinare la risposta al trattamento target sperimentale tramite MRI.

E.2.2

Secondary objectives of the trial

Secondary aims include: 1) the evaluation of toxicity during the treatment graded according to NCI CTCAE v 3.0 2) to assess whether tumor specimens harbouring microdeletion of the NF1 gene (constitutional or aquired) show specific characteristics which can be correlated with the patients' response to the treatment; thus allowing the setting of more tailored treatment of NF1 microdeleted patiens that; despite beeing a minority of all NF1 patients, has an enhanced risk to develop tumors (De Raedt et al., 2003); 3) to analyze constitutional DNA mutation in order to assess whether there are correlations between genotype, the risk of developing large neurofibromas, and tumor rensponse to drug; 4) to assess whether previously described increase in the serum levels of SCF.

Secondari: determinare la tossicità durante il trattamento; determinare la modificazione delle scale di deficit neurologico e di qualità di vita durante il trattamento; determinare se i pazienti con sindrome da microdelezione del gene NF1 e con tumore abbiano caratteristiche specifiche che possano essere correlabili alla risposta al trattamento; determinare la variazione dei livelli serici del ligando di c-KIT (SCF) durante il trattamento.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

OTHER SUBSTUDIES:
ancillary study assessment of CEC and CEP blood levels in patients. (Vers. 1.0 of 09.02.2012)

ALTRI SOTTOSTUDI:
studio ancillare sulle cellule endoteliali circolanti (CEC) e i progenitori endoteliali circolanti (CEP) e su altre popolazioni cellulari circolanti. Vers. 1.0 del 09/02/2012

E.3

Principal inclusion criteria

clinical diagnosis of NF1 according US National Institute of Health Consensus criteria, age at entry >3 < 65, and the presence of a measurable disabling or disfiguring plexiform neurofiroma that is not amenable to total surgical resection. Disabling PNF is defined as a tumor causing motor weakness by compression of the spinal cord or pain due to infiltration of spinal roots or limitation of limb mobility due to local mass effect. Disfiguring PNF is defined as an infiltranting tumor in the head and neck region with major cosmetic impairment, resulting in distress to the patient. Patients have to have a Lasky (children < 10 years) or Karnofsky (patients > 10 years) performance levels > 50. Radiographic progression is not a necessity for patient entry.

•diagnosi clinica di neurofibromatosi di tipo 1 in accordo con i criteri consenso del US National Institute of Health; •età di ingresso nello studio compresa tra 3 e 65 anni; •presenza di almeno un neurofibroma plessiforme (PNF) disabilitante o sfigurante il paziente, e localizzazione del tumore tale da rendere la rimozione chirurgica difficilmente praticabile. Un PNF viene definito disabilitante quando il tumore causa deficit motorio o dolore per compressione delle vie nervose o limitazione funzionale dovuta ad un effetto massa locale. Un PNF è definito sfigurante quando il tumore localizzato in testa e nel collo provoca un danno estetico maggiore al paziente. •indici di Lasky (bambini con meno di 10 anni) o di Karnofsky (pazienti con più di 10 anni) >50; •esame istologico probante la diagnosi di neuro fibroma plessiforme, disponibilità di tessuto tumorale per l’analisi l’espressione di c-KIT l sul tumore. •bilirubina totale <1,5 x ULN, SGOT e SGPT <2.5 x UNL, creatinina <1,5 x ULN, ANC> 1,5 x 109 / L, piastrine> 100 x 109 / L; •test di gravidanza negativo entro 7 giorni prima di iniziare la somministrazione del farmaco in studio per le pazienti di sesso femminile in età fertile; • consenso informato scritto.

E.4

Principal exclusion criteria

Patients undergoing radiation,chemotherapy, hormonal therapy, directed to the tumor or immunotherapy were excluded from partecipation. Other exclusion criteria are the presence of an active optic glioma or other tumor requiring radiation or chemotherapy.

• pazienti senza altri tumori maligni primari da meno di 5 anni, eccetto i casi in cui il tumore maligno primario non sia attualmente né clinicamente significativo e non richieda un intervento attivo, o il tumore maligno primario sia un cancro delle cellule basali della pelle o un carcinoma in situ della cervice. L’esistenza di una qualsiasi altra malattia maligna non è permessa; • pazienti con problemi cardiaci di grado III/IV, come definiti dai criteri di New York Heart Association. (cioè, insufficienza cardiaca congestizia, infarto miocardico entro 6 mesi dall’inizio del trattamento); • pazienti con nota metastasi al cervello; • ;pazienti sottoposti a chemioterapia nelle 4 settimane (6 settimane per nitrosourea o mitomicina-C) precedenti l’ingresso nello studio, a meno che la malattia stia progredendo rapidamente; • pazienti che hanno precedentemente ricevuto radioterapia superiore al 25% del midollo osseo; • pazienti che hanno subito un importante intervento chirurgico nelle 2 settimane precedenti l'ingresso nello studio.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with stable tumors volume.

proporzione di pazienti con volume stabile del tumore target (variazioni ≤25% del volume del tumore analizzato mediante MRI)

E.5.1.1

Timepoint(s) of evaluation of this end point

3, 6 and 12 months

3, 6 e 12 mesi

E.5.2

Secondary end point(s)

- tossicity - modification of neurological and quality of life scale - proportion of patiens with microdeletion of NF1 gene - SCF level in patiens

• profilo di tossicità; • modificazione delle scale di deficit neurologico e di qualità di vita a 3, 6 mesi e 12 mesi; • proporzione di pazienti con microdelezione e loro caratteristiche cliniche; • livelli serici del ligando di c-KIT (SCF) nei pazienti con neuro fibroma

E.5.2.1

Timepoint(s) of evaluation of this end point

3, 6 and 12 months

3, 6 e 12 mesi

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

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

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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.8.6 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

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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)

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.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)

Normal clinical practice

Normale pratica clinica

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

2012-04-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-03-07

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

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