Clinical Trials Register

Summary
EudraCT Number:	2016-005238-31
Sponsor's Protocol Code Number:	TENEC
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:	2021-06-08
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

2016-005238-31

A.3

Full title of the trial

A Phase II Single Arm Trial Evaluating the Efficacy and Safety of Temozolomide for Second-Line Treatment of Neuroendocrine Carcinomas Progressing after First-Line Platinum- based Therapy

Studio di Fase II per la valutazione dell¿efficacia e la sicurezza della Temozolomide in seconda linea nei pazienti affetti da Tumore Neuroendocrino di origine pancreatica, gastrointestinale o polmonare in progressione dopo precedente linea di chemioterapia a base di platino.

A.3.1

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

A Phase II Single Arm Trial Evaluating the Efficacy and Safety of Temozolomide for Second-Line Treatment of Neuroendocrine Carcinomas Progressing after First-Line Platinum- based Therapy

A.3.2

Name or abbreviated title of the trial where available

TENEC

A.4.1

Sponsor's protocol code number

TENEC

A.5.4

Other Identifiers

Name:

TENEC

Number:

TENEC

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 NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
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	Fondi istituzionali
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	Istituto Tumori di Napoli
B.5.2	Functional name of contact point	Oncologia Medica Addominale
B.5.3	Address:
B.5.3.1	Street Address	Via Mariano Semmola
B.5.3.2	Town/ city	Napoli
B.5.3.3	Post code	80131
B.5.3.4	Country	Italy
B.5.4	Telephone number	0815903680
B.5.5	Fax number	0815903680
B.5.6	E-mail	s.tafuto@istitutotumori.na.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	TEMODAL - 5 MG CAPSULA RIGIDA 1 FLACONE 20 CAPSULE USO ORALE
D.2.1.1.2	Name of the Marketing Authorisation holder	MERCK SHARP e DOHME LIMITED
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	temodal
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.3.11 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

Neuroendocrine Carcinomas

PAZIENTI CON NEOPLASIA NEUROENDOCRINA INDIFFERENZIATA DI G3

E.1.1.1

Medical condition in easily understood language

Neuroendocrine Carcinomas

PAZIENTI CON NEOPLASIA NEUROENDOCRINA INDIFFERENZIATA DI G3

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.1.2 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

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy and safety of Temozolomide for second-line treatment of Neuroendocrine Carcinomas progressing after first-line Platinum-based therapy

Valutare l¿efficacia e la sicurezza di Temozolomide in II linea di pazienti affetti da carcinoma neuroendocrino progrediti dopo precedente linea di trattamento

E.2.2

Secondary objectives of the trial

To assess the clinical benefit of Neuroendocrine Carcinomas progressing after first-line Platinum-based therapy

Valutare il clinical benefit dei pazienti affetti da carcinoma neuroendocrino progrediti dopo precedente linea di trattamento

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Signed informed consent prior to initiation of any study-specific procedures or treatment, as confirmation of the patient’s awareness and willingness to comply with the study requirements.
- Patients =18 years of age.
- Histologically confirmed Metastatic Neuroendocrine Carcinoma (Ki67>20% Ki67 must be quantified in percentage) with documented progression of disease per investigator assessment following or during first-line platinum-based treatment.
- ECOG performance status (PS) of 0-2.
- At least 28 days since prior radiation therapy or surgery and recovery from treatment.
- Patients must have measurable disease which must be evaluable per RECIST v1.1.
- Estimated life expectancy of =12 weeks.

- Firma del consenso informato prima di iniziare qualsiasi procedura o trattamenti specifici di studio, a conferma della consapevolezza e la volontà di rispettare i requisiti di studio del paziente.
- I pazienti = 18 anni di età.
-Diagnosi istologicamente confermata di carcinoma neuroendocrino metastatico (Ki67> 20% Ki67 deve essere quantificato in percentuale)
- ECOG performance status (PS) di 0-2.
- Ogni trattamento preceedente deve essere stato interrotto almeno 28 giorni prima dall’inizio della somministrazione del farmaco in studio.
- I soggetti devono mostrare evidenza di progressione di malattia, in accordo alle linee-guida RECIST 1.1
- L'aspettativa di vita stimata di =12 settimane.

E.4

Principal exclusion criteria

- Patients < 18 years of age
- Diagnosis of well differentiated G1/G2 NEN
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would prevent the patient from meeting the study requirements.
- Serious active infection requiring i.v. antibiotics and/or hospitalization at study entry.
- Patients who are treated with any medicinal product that contraindicates the use of the study drug, may interfere with the planned treatment, affects patient compliance or puts the patient at high risk for treatment-related complications.
- Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly). Perimenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
- Patients with meningeal carcinomatosis
- Patients with organ allografts requiring immunosuppression
- Patients with known positive HIV status
- Patients with a hypersensitivity to Temozolomide or Dacarbazine
- Any laboratory values at baseline as follows:
Hematology:
a. ANC <1.5x109/L or 1500/mm3
b. Platelet count <100x109/L
c. Hemoglobin <8 g/dL (Note: hemoglobin levels may be supported by transfusion or erythropoietin or other approved hematopoietic growth factors).
Coagulation:
a. INR >1.5 except for patients on stable anticoagulant therapy
b. aPTT =1.5 times ULN or greater than the lower limit of the therapeutic range
Note: The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of Day 1, Cycle 1.
Serum chemistry:
a. Total bilirubin >1.5 times ULN
b. AST or ALT >2 times ULN (>5 times ULN for patients with known
liver involvement)
c. ALP >2 times ULN (>5 times ULN for patients with known liver
involvement and >7 times ULN for patients with known bone
involvement).

I pazienti <18 anni di età al momento della firma del consenso informato
- Disturbi psichiatrici o di dipendenza o altre condizioni che, a giudizio dello sperimentatore, impedirebbero al paziente di soddisfare i requisiti di studio.
- Infezione attiva grave che richieda l’impiego di antibiotici i.v. e / o il ricovero in ospedale all'inizio dello studio.
- I pazienti in trattamento con qualsiasi terapia controindicata al farmaco in studio, che possa interferire con il trattamento previsto, e/o influenzi la compliance del paziente e/o metta il paziente in condizioni rischiose per il suo stato di salute.
- Gravidanza e allattamento. Tutti i soggetti femminili devono avere un test di gravidanza su siero o urine negativo (sensibilità minima 25 IU/L o unità equivalenti di gonadotropina corionica umana (ß-HCG) alla visita basale (e/o entro le 7 giorni precedenti la prima dose del farmaco in studio). Le donne fertili (definite con < 2 anni dall’ultimo ciclo mestruale e non chirurgicamente sterili) che non usino un metodo contraccettivo accettabile (ad es: un dispositivo intrauterino, un metodo a doppia barriera quale preservativo + spermicida o preservativo + diaframma con spermicida, un impianto contraccettivo, un contraccettivo orale o avere un partner vasectomizzato con azoospermia confermata). I soli soggetti che saranno esentati da tale requisito sono le donne in post-menopausa (definite come donne che siano in condizioni di amenorrea per almeno 12 mesi consecutivi, di età appropriata e in assenza di altre sospette o note cause primarie) o soggetti che siano sterilizzati chirurgicamente o che abbiano una sterilità dimostrata in altro modo (ad es.: legatura bilaterale delle tube con chirurgia almeno un mese prima dell’inizio del trattamento con il farmaco di studio, isterectomia oppure ooforectomia bilaterale con chirurgia almeno un mese prima dell’inizio del trattamento con il farmaco di studio).
- I pazienti con carcinomatosi meningea
- I pazienti con trapianti d'organo che richiedono immunosoppressione
- Pazienti HIV positivi
- I pazienti con ipersensibilità a Temozolomide o dacarbazina
- Tutti i valori di laboratorio al basale come segue:
- inadeguata funzione midollare:
- Conta assoluta dei neutrofili <1.5x109/L or 1500/mm3
- Conta delle piastrine <100x109/L
- Emoglobina <8 g/dL (Nota: I livelli di emoglobina possono essere supportati da terapia trasfusionale, trattamento con eritropoietine o altri fattori di crescita ematopoietici) F
- inadeguata funzione della coagulazione :
- INR >1.5 esclusi I pazienti in terapia con anticoagulanti
- aPTT =1.5 volte il limite superiore di normalità (ULN) o maggiore del limite inferiore al range terapeutico
Nota: L'uso di anticoagulanti orali o parenterali è consentita finché l'INR o aPTT è entro limiti terapeutici e il paziente è stato trattato con una dose
di anticoagulanti per almeno due settimane antecedenti al momento del giorno 1, ciclo 1.

- Bilirubina Totale >1.5 volte il limite superiore di normalità (ULN)

- AST or ALT >2 volte il limite superiore di normalità (ULN) (oppure > 5 volte per il limite superiore di normalita` ULN se il soggetto presenta metastasi epatica).
- ALP >2 volte il limite superiore di normalità (ULN) (oppure > 5 volte per il limite superiore di normalita` ULN se il soggetto presenta metastasi epatica e <7 volte per I pazienti con metastasi ossee).

- Inadeguata funzione renale:
- Creatinine clearance < 35 mL/min

E.5 End points

E.5.1

Primary end point(s)

- Overall response rate (ORR)

E.5.1.1

Timepoint(s) of evaluation of this end point

9 WEEKS

9 SETTIMANE

E.5.2

Secondary end point(s)

- Clinical Benefit Rate (CBR)
- Second Line Progression Free Survival (PFS)
- Overall survival (OS)
- 1 Year OS
- Safety and tolerability
- Duration of response
- Quality of Life (QoL)

- Clinical Benefit Rate (CBR)
- Second Line Progression Free Survival (PFS)
- Overall survival (OS)
- 1 anno OS
- Sicurezza e tollerabilit¿
- Durata della Risposta
- Quality of Life (QoL)

E.5.2.1

Timepoint(s) of evaluation of this end point

9 WEEKS

9 SETTIMANE

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

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

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)

BEST 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

2017-03-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-18

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