Clinical Trials Register

Summary
EudraCT Number:	2020-005393-10
Sponsor's Protocol Code Number:	IEO1411
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:	2021-08-17
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

2020-005393-10

A.3

Full title of the trial

An Italian multicenter phase II trial of Metronomic Temozolomide in unfit patients with advanced neuroendocrine neoplasms (NENs): MeTe study

Studio italiano multicentrico di fase II con Temozolomide metronomica in pazienti "fragili" con neoplasia neuroendocrina avanzata (NENs): MeTe study

A.3.1

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

An Italian multicenter trial with Temozolomide taken daily at low doses continuously in patients with well differentiated neuroendocrine neoplasia (NENs) and in a clinical frailty status

Studio italiano multicentrico con Temozolomide assunta quotidianamente a basse dosi continuative in pazienti con neoplasia neuroendocrina ben differenziata (NENs) ed in condizioni cliniche di fragilità

A.3.2

Name or abbreviated title of the trial where available

MeTe Study

A.4.1

Sponsor's protocol code number

IEO1411

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 EUROPEO DI ONCOLOGIA
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Istituto Europeo di Oncologia
B.5.2	Functional name of contact point	Ufficio Studi Clinici e Attività Re
B.5.3	Address:
B.5.3.1	Street Address	via Ripamonti 435
B.5.3.2	Town/ city	Milano
B.5.3.3	Post code	20141
B.5.3.4	Country	Italy
B.5.4	Telephone number	0257489848
B.5.6	E-mail	ufficio.studiclinici@ieo.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	TEMOZOLOMIDE SUN - 20MG - CAPSULA RIGIDA - USO ORALE - BLISTER (ALU/ALU) 5X1 CAPSULE (DOSE UNITARIA)
D.2.1.1.2	Name of the Marketing Authorisation holder	SUN PHARMACEUTICAL INDUSTRIES (EUROPE) B.V.
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	Temozolomide
D.3.2	Product code	[Temozolomide]
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	Temozolomide
D.3.9.1	CAS number	85622-93-1
D.3.9.2	Current sponsor code	na
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	20
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 well differentiated neuroendocrine neoplasia (NENs) not eligible for active antitumoral treatments due to their clinical conditions.

Pazienti con neoplasia neuroendocrina ben differenziata (NENs) che, per le condizioni cliniche globali, sono generalmente esclusi dai trattamenti oncologici attivi.

E.1.1.1

Medical condition in easily understood language

Patients with well differentiated neuroendocrine neoplasia (NENs) not eligible for active antitumoral treatments due to their clinical conditions.

Pazienti con neoplasia neuroendocrina ben differenziata (NENs) che, per le condizioni cliniche globali, sono generalmente esclusi dai trattamenti oncologici attivi.

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10057270
E.1.2	Term	Neuroendocrine carcinoma
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

Progression free survival (PFS).

Sopravvivenza libera da progressione di malattia (PFS).

E.2.2

Secondary objectives of the trial

• Objective response rate (ORR) that means complete response (CR) + partial response (PR) in progressive, metastatic, low grade NENs.
• Duration of response.
• Overall survival (OS).
• Safety.
• Quality of life (QoL)
• Centralized evaluation of O6-methylguanine-DNA-methyltransferase (MGMT) status in tumor tissue to correlate clinical outcomes and MGMT status and validate the method of MGMT determination.

• Tasso di risposta obiettiva (ORR) intesa come risposta completa (CR) + risposta parziale (PR) in pazienti NENs di basso grado metastatici in progressione.
• Durata della risposta.
• Sopravvivenza globale (OS).
• Sicurezza.
• Qualità della vita (QoL)
• Valutazione centralizzata dello stato di O6-metilguanina-DNA-metiltransferasi (MGMT) neltessuto tumorale per correlare lo stato di MGMT con gli esiti clinici e validare la metodica dideterminazione di MGMT.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Age > 18 years;
• Histologically proven diagnosis of low grade GEP-NENs (in accordance with WHO 2019 classification), bronchial carcinoids (in accordance with the Travis classification), low grade of unknown primary sites NENs;
• Advanced disease (unresectable locally advanced or metastatic);
• ECOG performance status 2 and/or moderate medullary impairment (Hb concentration <10-8 gr/dl; WBC <3000-2000/mm3; platelets <75000-50000/mm3; neutrophil count <1500- 1000/mm3); renal failure (eGFR o CrCl 30-59 ml/min – G2) and/or moderate liver failure (Child B 7-9) and/or severe comorbidities and/or > 3 prior systemic antitumor therapies (apart from SSA);
• Functioning/non functioning;
• Morphological progressive disease (CT scan or MRI);
• Clinical progression (as judged by the investigator).

• Età> 18 anni;
• Diagnosi istologica di GEP-NEN di basso grado (includo morfologia e Ki67 secondo la classificazione WHO 2019), carcinoidi bronchiali (secondo la classificazione Travis del 2015), NEN a basso grado con siti primari ignoti;
• Malattia avanzata (non resecabile localmente avanzato o metastatico);
• Performance status ECOG 2 e / o insufficienza midollare moderata (Hb concentration <10-8 gr/dl; WBC <3000-2000/mm3; platelets <75000-50000/mm3; neutrophil count <1500- 1000/mm3); insufficienza renale (eGFR o CrCl 30-59 ml / min - G2) e / o insufficienza epatica moderata (Child B 7-9) e / o gravi comorbidità e / o > 3 precedenti terapie antitumorali (escluso SSA);
• Funzionante / non funzionante;
• Malattia morfologica progressiva (TC o RM);
• Progressione clinica (secondo il giudizio dello sperimentatore).

E.4

Principal exclusion criteria

• Patients pretreated with Temozolomide
• Are Women of Child-Bearing Potential (WOCBP) and men who are able to father a child, unwilling to use adequate contraception prior to trial entry, for the duration of trial participation and for at least 28 days 2 weeks after treatment has ended. Adequate methods of contraception and Women of Child-Bearing Potential; WOCBP childbearing potential who are nursing or are pregnant or do not agree to submit to pregnancy testing required by this protocol
• Patients that did not sign written informed consent prior to admission into the trial that is consistent with International Conference on Harmonisation (ICH)- Good Clinical Practice (GCP) guidelines and local law
• Known active hepatitis B infection (defined as presence of Hepatitis B (HepB) sAg and/or HepB DNA), active Hepatitis C (HEP C) infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV) carrier.

• Pazienti pretrattati con Temozolomide.
• Donne in età fertile (WOCBP) e uomini non disposti a usare un'adeguata contraccezione prima dell'ingresso nello studio, per la durata della partecipazione allo studio e per almeno 28 giorni 2 settimane dopo la fine del trattamento. Metodi contraccettivi adeguati e donne in età fertile; Potenziale fertile WOCBP in allattamento o in gravidanza o che non accetta di sottoporsi ai test di gravidanza richiesti da questo protocollo
• Pazienti che non hanno firmato il consenso informato scritto prima dell'ammissione allo studio, in linea con le linee guida della Conferenza internazionale sull'armonizzazione (ICH) - Good Clinical Practice (GCP) e della legislazione locale
• Infezione da epatite B attiva nota (definita come presenza di epatite B (HepB) sAg e / o DNA HepB), infezione da epatite C attiva (HEP C) (definita come presenza di RNA Hep C) e / o virus dell'immunodeficienza umana noto (HIV ).

E.5 End points

E.5.1

Primary end point(s)

• Progression free survival (PFS)

• Sopravvivenza libera da malattia (PFS)

E.5.1.1

Timepoint(s) of evaluation of this end point

Every month during treatment period, every 3 months for the first 1 year after the end of the treatment, and then every 6 months for 1 year.

Ogni mese per il periofo di trattamento, ogni 3 mesi per il primo 1 anno dopo la fine del trattamento e ogni 6 mesi per 1 anno.

E.5.2

Secondary end point(s)

• Objective response rate (ORR) that means complete response (CR) + partial response (PR) in
progressive, metastatic, low grade NENs.
• Duration of response.
• Overall survival (OS).
• Safety.
• Quality of life (QoL)
• Centralized evaluation of O6-methylguanine-DNA-methyltransferase (MGMT) status in tumor tissue to correlate clinical outcomes and MGMT status and validate the method of MGMT determination

• Tasso di risposta obiettiva (ORR) intesa come risposta completa (CR) + risposta parziale (PR) in
pazienti NENs di basso grado metastatici in progressione.
• Durata della risposta.
• Sopravvivenza globale (OS).
• Sicurezza.
• Qualità della vita (QoL)
• Valutazione centralizzata dello stato di O6-metilguanina-DNA-metiltransferasi (MGMT) nel tessuto tumorale per correlare lo stato di MGMT con gli esiti clinici e validare la metodica di determinazione di MGMT

E.5.2.1

Timepoint(s) of evaluation of this end point

Every month during treatment period, every 3 months for the first 1 year after the end of the treatment, and then every 6 months for 1 year.

Ogni mese per il periofo di trattamento, ogni 3 mesi per il primo 1 anno dopo la fine del trattamento e ogni 6 mesi per 1 anno.

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.6 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

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)

Patients will be treated in accordance with the standard of care

I pazienti riceveranno terapia in accordo con lo standard of care.

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

2021-09-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-19

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