Clinical Trials Register

Summary
EudraCT Number:	2012-004539-22
Sponsor's Protocol Code Number:	11-2012
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-01-11
Trial results	View 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

2012-004539-22

A.3

Full title of the trial

An open label, single arm, phase II study to evaluate the activity and toxicity of Panitumumab in pre-treated patients with advanced well differentiated neuroendocrine tumor (G1 and G2)

Studio di fase II in aperto per valutare l'attivita' e la tossicità di Panitumumab nei pazienti pre-trattati affetti da tumore neuroendocrino ben differenziato (G1 e G2)

A.3.1

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

Panitumumab in patients with neuroendocrine tumor

Utilizzo di Panitumumab nei pazienti con tumore neuroendocrino

A.3.2

Name or abbreviated title of the trial where available

Panitumumab and NETs

A.4.1

Sponsor's protocol code number

11-2012

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	I.T.M.O. - ITALIAN TRIALS IN MEDICAL ONCOLOGY
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	Amgen Dompè
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	Gruppo ITMO
B.5.2	Functional name of contact point	Ufficio Assistenza Ricerca Clinica
B.5.3	Address:
B.5.3.1	Street Address	via Modigliani 10
B.5.3.2	Town/ city	Monza
B.5.3.3	Post code	20900
B.5.3.4	Country	Italy
B.5.4	Telephone number	039.8379931
B.5.5	Fax number	039.8379951
B.5.6	E-mail	gruppo.itmo@tiscali.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	Vectibix
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PANITUMUMAB
D.3.9.1	CAS number	339177-26-3
D.3.9.4	EV Substance Code	SUB25390
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Anticorpo monoclonale

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

Well differentiated neuroendocrine tumor (G1 and G2)

Tumore neuroendocrino ben differenziato (G1 e G2)

E.1.1.1

Medical condition in easily understood language

Neuroendocrine tumor

Tumore neuroendocrino

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	PT
E.1.2	Classification code	10052399
E.1.2	Term	Neuroendocrine tumour
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

To evaluate the activity and efficacy of panitumumab in metastatic or locally advanced well differentiated neuroendocrine tumor after somatostatine analogues and possible chemotherapy.

Valutare l’attività e l’efficacia del panitumumab nel tumore neuroendocrino ben differenziato metastatico o localmente avanzato dopo trattamento con analoghi della somatostatina ed eventuale chemioterapia.

E.2.2

Secondary objectives of the trial

To evaluate activity (on further parameters: see §2.4), efficacy and tolerability of panitumumab in metastatic or locally advanced well differentiated neuroendocrine tumor after somatostatine analogues and chemotherapy.

Ulteriori valutazioni di attività, valutazione dell’efficacia e della tollerabilità del trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Histological diagnosis of well-differentiated neuroendocrine tumor (G1 and G2) of gastro-entero-pancreatic district or of unknown primary site. •Disease progression after treatment with somatostatin analogues •Previous treatment with everolimus, sunitinib or bevacizumab is admitted. •One chemotherapy is admitted. •Metastatic or locally advanced disease. •Male or female, age > 18 years. •Absence carcinoid syndrome. •ECOG performance status 0-1. •Expectancy of life > 6 months •Written informed consent •Adequate liver function as shown by: serum bilirubin ≤1.5 x ULN; ALT and AST < 2.5x ULN (< 5x ULN in patients with liver metastases) •Adequate bone marrow function: ANC > 1.5 x 109/L;PLT > 100 x 109/L; Hb > 9 g/dL •Creatinine clearance > 50 ml/min •Magnesium and calcium > lower limit of normal •At least one measurable lesion at CT scan as defined by RECIST •Women of childbearing potential must have had a negative serum or urine pregnancy test within 7 days prior to the administration of the study treatment start, and must use an acceptable form of contraception

•Diagnosi istologica di tumore neuroendocrino ben differenziato (G1 e G2) del tratto gastro-entero-pancreatico o a sede primitiva ignota •Progressione di malattia dopo trattamento con analoghi della somatostatina •E’ ammesso un precedente trattamento con farmaci biologici (everolimus, sunitinib o bevacizumab) •E’ ammessa una linea di chemioterapia •Malattia metastatica o localmente avanzata •Maschi o femmine di età > 18 anni •Assenza di sindrome da carcinoide •ECOG performance status 0-1 •Aspettativa di vita > 6 mesi •Consenso informato scritto •Funzionalità epatica adeguata: bilirubina totale ≤1.5 x ULN; ALT e AST < 2.5x ULN (< 5x ULN in pazienti con metastastasi epatiche) •Adeguata funzionalità midollare: ANC > 1.5 x 109/L;PLT > 100 x 109/L; Hb > 9 g/dL •Creatinina clearance > 50 ml/min •Magnesio e calcio con valori > i limiti inferiori di norma •Almeno una lesione misurabile secondo i criteri RECIST •Donne in età fertile devono avere un test di gravidanza negativo eseguito nei 7 giorni precedenti l’attivazione del trattamento. Tutti i pazienti devono utilizzare un adeguato metodo contraccettivo

E.4

Principal exclusion criteria

•Patients with a known hypersensitivity to panitumumab •Histological diagnosis of poorly differentiated neuroendocrine carcinoma (G3) •Histological diagnosis of lung neuroendocrine tumors (typical or atypical carcinoid, small cell lung cancer, large cell neuroendocrine carcinoma) •Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 12 months prior to first study treatment, serious uncontrolled cardiac arrhythmia; severely impaired lung function; uncontrolled diabetes; any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study; non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment, such as severe hypertension that is not controlled with medical management and thyroid abnormalities due to which thyroid function cannot be maintained in the normal range by medication; liver disease such as cirrhosis, decompensated liver disease, chronic active hepatitis or chronic persistent hepatitis; fatal or life-threatening autoimmune and ischemic disorders; uncontrolled hyperlipidemia •History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan. •Patients with serious neurological or psychiatric disorders •Patients with central nervous system (CNS) metastases •Patients who have a history of another primary malignancy with the exception of basal or squamous cell skin cancer, in situ cancer, and any cancer from which the patient has been disease free for 5 years •Immunocompromised patients, including positive HIV test. An HIV test is not required to enter the study •Female patients who are pregnant or breast feeding •Patients of reproductive potential who are not using appropriate contraceptive methods. Appropriate forms of contraception are: IUD, oral or depot contraceptive or the barrier method plus spermicide.

•Pazienti con ipersensibilità nota al Panitumumab •Diagnosi istologica di carcinoma neuroendocrino scarsamente differenziato (G3) •Diagnosi istologica di tumore neuroendocrino del polmone (carcinoide tipico o atipico, microcitoma, carcinoma neuroendocrino a grandi cellule) •Pazienti che abbiano ogni condizione medica severa o incontrollata che possa condizionare la loro partecipazione allo studio. Per es: angina instabile, cardiopatie sintomatiche, I.M.A. nei dodici mesi precedenti l’ingresso in studio, aritmie severe incontrollate, severe alterazioni della funzionalità polmonare, diabete incontrollato, infezioni attive, ipertensione incontrollata, anomalie tiroidee che impediscono un normale controllo della funzione tiroidea, patologie epatiche non controllate (es.: cirrosi, epatite cronica attiva o epatite acuta), disordini ischemici o autoimmuni condizionanti rischio di vita, iperlipidemia non controllata •Storia di malattia polmonare interstiziale documentata •Pazienti con disordini neurologici o psichiatrici severi •Pazienti con metastasi cerebrali •Pazienti con anamnesi positiva per altra neoplasia (fatta eccezione per carcinoma basocellulare o spino cellulare della cute o cancro in situ) se non sono trascorsi 5 anni senza evidenza di recidiva •Pazienti immunocompromessi incluso pazienti con test HIV positivo. Il test HIV non è richiesto per l’ingresso in studio. •Donne in gravidanza o in allattamento. •Pazienti in età riproduttiva che non facciano uso di adeguato metodo anticoncezionale. Forme appropriate di contraccezione sono: IUD, contraccettivi orali o depot, metodo di barriera + spermicida.

E.5 End points

E.5.1

Primary end point(s)

Activity is defined as Non-progression rate, (RECIST criteria version 1.1), as evaluated at 6 months.

L’attività è definita attraverso il tasso di non-progressione, (criteri RECIST v.1.1), valutato a 6 mesi.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mesi

E.5.2

Secondary end point(s)

Best objective response (CR + PR according to RECIST criteria version 1.1): complete plus partial responses, as evaluated at 6 months Biochemical response (changes of tumor marker values) Time to progression (TTP) and overall survival (OS), as estimated by the Kaplan-Meier method. Adverse reaction definition and grading according to CTC-AE v.3.0

Miglior risposta obiettiva (CR+PR secondo criteri RECIST 1.1): risposte complete e parziali valutate a 6 mesi Risposta biochimica (cambiamento nel tempo degli indicatori biochimici di malattia) Tempo di progressione (TTP) e sopravvivenza globale (OS), secondo il metodo di Kaplan-Meier. Tollerabilità del trattamento, secondo CTC-AE v.3.0

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

24 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

Yes

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

Yes

E.8.2.3.1

Comparator description

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

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)

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.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)

At the end of the study, patients will be followed regularly according to good clinical practice

Al termine della partecipazione allo studio, i pazienti saranno seguiti regolarmente secondo le norme di buona 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

2013-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-01-24

P. End of Trial
P.	End of Trial Status	Completed

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