Clinical Trials Register

Summary
EudraCT Number:	2021-006570-23
Sponsor's Protocol Code Number:	FAPI-POLMONE-2021
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:	2021-12-07
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2021-006570-23

A.3

Full title of the trial

The Role Of The New Promising Oncological Pet/Ct Tracer [68Ga] Ga-Fapi For Staging Lung Cancer: A Preliminary Study

Il ruolo del nuovo promettente radiofarmaco oncologico PET/TC [68Ga]-FAPI nella stadiazione del carcinoma polmonare: uno studio preliminare

A.3.1

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

The Role Of The New Promising Oncological Pet/Ct Tracer [68Ga] Ga-Fapi For Staging Lung Cancer: A Preliminary Study

Il ruolo del nuovo promettente radiofarmaco oncologico PET/TC [68Ga]-FAPI nella stadiazione del carcinoma polmonare: uno studio preliminare

A.3.2

Name or abbreviated title of the trial where available

FAPI-POLMONE-2021

A.4.1

Sponsor's protocol code number

FAPI-POLMONE-2021

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	AOU DI BOLOGNA POLICLINICO S.ORSOLA-MALPIGHI
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	Programma Ricerca finalizzata Emilia-Romagna (FINRER)
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	IRCCS AOU di Bologna, Policlinico di S.Orsola
B.5.2	Functional name of contact point	U.O. Medicina Nucleare
B.5.3	Address:
B.5.3.1	Street Address	via Albertoni 15
B.5.3.2	Town/ city	Bologna
B.5.3.3	Post code	40138
B.5.3.4	Country	Italy
B.5.6	E-mail	lucia.zanoni@aosp.bo.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	No
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	68Ga-FAPI-46
D.3.2	Product code	[68Ga-FAPI-46]
D.3.4	Pharmaceutical form	Solution for injection
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	[68Ga]Ga-FAPI-46
D.3.9.2	Current sponsor code	[68Ga]Ga-FAPI-46
D.3.10	Strength
D.3.10.1	Concentration unit	MBq megabecquerel(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	150 to 250
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	Yes
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

suspected / newly diagnosed lung cancer in staging, patients already on a conventional staging diagnostic path (including FDG-PET / standard CT)

neoplasia polmonare sospetta/di nuova diagnosi in stadiazione, pazienti già inseriti in un percorso diagnostico di stadiazione convenzionale (incluso FDG-PET/TC standard)

E.1.1.1

Medical condition in easily understood language

suspected / newly diagnosed lung cancer in staging, already included in a conventional staging diagnostic path (including FDG-PET / standard CT)

neoplasia polmonare sospetta/di nuova diagnosi in stadiazione, già inseriti in un percorso diagnostico di stadiazione convenzionale (incluso FDG-PET/TC standard)

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	LLT
E.1.2	Classification code	10025064
E.1.2	Term	Lung carcinoma
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

The study aims to evaluate the diagnostic performance of PET / CT with 68Ga-FAPI, in patients with staging lung cancer, in the identification of disease locations by comparing the (overall) evaluation of the 68Ga-FAPI outcome. PET / CT with histological data

Lo studio si propone di valutare la performance diagnostica della PET/TC con 68Ga-FAPI, in pazienti con neoplasia del polmone in stadiazione, nell’identificazione di localizzazioni di malattia attraverso il confronto tra la valutazione (complessiva) dell’esito della 68Ga-FAPI PET/TC con il dato istologico

E.2.2

Secondary objectives of the trial

Evaluate: -Diagnostic performance of PET / CT with 68Ga-FAPI experimental radiopharmaceutical, on the basis of evaluation by region, in the setting of patients referred (only by conventional staging exams) to radical surgery, subjected, according to a normal diagnostic-assistance path, to histopathological evaluation and 1 year conventional clinical diagnostic follow-up; -positivity rate and concordance of 68Ga-FAPI PET / CT with conventional staging imaging (including 18F-FDG-PET / CT and diagnostic CT), in excluded patients from radical surgery; -performance of the semi-quantitative parameters of 68Ga-FAPI uptake in the staging of lung cancer. PET / CT with 68Ga-FAPI (in terms of TNM staging) could have led to a potential, only theoretical, change in diagnostic-therapeutic management to patients.

Valutare:-performance diagnostica della PET/CT con radiofarmaco sperimentale 68Ga-FAPI,sulla base di valutazione per regione,nel setting di pazienti indirizzati (solo dagli esami di stadiazione convenzionale)a chirurgia radicale,sottoposti,secondo normale percorso diagnostico-assistenziale,a valutazione istopatologica e a follow-up clinico-diagnostico convenzionale di 1 anno;-positivity rate e concordanza di 68Ga-FAPI PET/TC con l'imaging di stadiazione convenzionale,nei pazienti esclusi dalla chirurgia radicale;-performance dei parametri semi-quantitativi della captazione del 68Ga-FAPI nella stadiazione del carcinoma polmonare.-Al termine dello studio si vuole esplorare,nonostante i pazienti saranno trattati solo secondo esami di stadiazione della normale pratica clinica,se i risultati della PET/TC con 68Ga-FAPI(in termini di stadiazione TNM)avrebbero potuto portare a un potenziale,solo teorico,cambiamento nella gestione diagnostico-terapeutica dei pazienti.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Patients with suspected / newly diagnosed lung cancer in staging, already on a conventional staging diagnostic path (including FDG-PET / standard CT);
• Age =18 years
• Both sexes
• Signature of informed consent

• Pazienti con neoplasia polmonare sospetta/di nuova diagnosi in stadiazione, già inseriti in un percorso diagnostico di stadiazione convenzionale (incluso FDG-PET/TC standard);
• Età =18anni
• Entrambi i sessi
• Firma del consenso informato

E.4

Principal exclusion criteria

• Pregnant women. The state of pregnancy in women of childbearing potential will be ascertained by measuring ß-hCG
• Breastfeeding women
• Patients in emergency situations or unable to understand and want
• History of allergic reactions or hypersensitivity to the active substance, to any of the excipients, or to any of the components of the radiolabelled radiopharmaceutical
• Contraindication to PET / CT examination for patients unable to perform PET due to weight, claustrophobia or the inability to remain still for the duration of the examination
• Participation in a clinical trial in which an investigational drug was administered within 30 days or 5 half-lives before the study drug
• Patients with severely impaired renal function
• Patients with severely impaired liver function

• Donne in stato di gravidanza. Lo stato di gravidanza nelle donne potenzialmente fertili verrà accertato tramite la rilevazione della ß-hCG
• Donne in allattamento
• Pazienti in situazioni di emergenza o non in grado di intendere e di volere
• Anamnesi di reazioni allergiche o ipersensibilità al principio attivo, a uno qualsiasi degli eccipienti, o a uno qualsiasi dei componenti del radiofarmaco marcato
• Controindicazione all’esame PET/TC per pazienti non in grado di eseguire la PET a causa del peso, della claustrofobia o dell'incapacità di rimanere fermi per tutta la durata dell'esame
• Partecipazione ad uno studio clinico in cui è stato somministrato un farmaco sperimentale entro 30 giorni o 5 emivite prima del farmaco in studio
• Pazienti con funzione renale severamente compromessa
• Pazienti con funzione epatica severamente alterata

E.5 End points

E.5.1

Primary end point(s)

In the primary and secondary objectives, the endpoints of the performance of PET / CT examinations with 68Ga-FAPI will be categorized as positive or negative, based on the independent evaluation of at least two nuclear doctors experts in oncology imaging. In the event of a discrepancy between the two readers or a finding of inconclusive findings, a consensus will be reached based on the opinion of a third expert nuclear doctor, also independent.
The findings will be evaluated by nuclear physicians as positive for 68Ga-FAPI uptake if the SUVmax of the radiopharmaceutical in a specific VOI that fully includes the lesion is> the SUVmean of the background (surrounding tissues) which will be calculated in a VOI of 1 cm.
The findings will be judged by nuclear doctors to be negative for 68Ga-FAPI uptake if they do not show uptake of the radiopharmaceutical or an uptake lower than the surrounding background (SUVmax doubtful finding / SUVmean of the background =1.
The results of the PET / CT survey with 68Ga-FAPI will be evaluated by nuclear doctors as VP / FP / VN / FN based on the result of the histological examination, when available; otherwise based on the comparison with conventional staging investigations (CT and PET / CT with 18F-FDG) and with the clinical-instrumental follow-up in the 12 months following the experimental investigation.
Sensitivity, specificity, accuracy, PPV and NPV will be calculated on an analysis by patient and by region, to evaluate the performance of PET / CT with 68Ga-FAPI.
The accuracy of PET / CT with 68Ga-FAPI will be calculated with the following statistical formula:
(TRUE POSITIVE + TRUE NEGATIVE) / TOTAL PATIENTS
The sensitivity of PET / CT with 68Ga-FAPI will be calculated with the following statistical formula:
TRUE POSITIVE / (TRUE POSITIVE + FALSE NEGATIVE)
The specificity of PET / CT with 68Ga-FAPI will be calculated with the following statistical formula:
TRUE NEGATIVE / (TRUE NEGATIVE + FALSE POSITIVE)
The negative predictive value of PET / CT with 68Ga-FAPI will be calculated with the following statistical formula:
TRUE NEGATIVE / (TRUE NEGATIVE + FALSE NEGATIVE)
The positive predictive value of PET / CT with 68Ga-FAPI will be calculated with the following statistical formula:
TRUE POSITIVE / (TRUE POSITIVE + FALSE POSITIVE)

The performance of the continuous semiquatitative PET variables (for example SUVmax and TBR) (secondary objective) will be evaluated in relation to the result of the histological examination, when available; otherwise on the basis of the comparison with conventional staging investigations (CT and PET / CT with [18F] FDG) and with the clinical-instrumental follow-up in the 12 months following the experimental investigation.
In non-surgical patients, the positivity rate of PET / CT with 68Ga-FAPI and the agreement with conventional staging imaging will be calculated.
In patients referred for radical surgery, the results of PET / CT (T and N) will be validated by the histopathological examination, performed according to the normal care pathway, of the surgical samples.
The clinical-diagnostic follow-up, performed routinely by the thoracic surgery unit for at least 1 year after surgery, will be used as a reference standard to validate the results of PET in sites not treated surgically.
At the end of the study, the hypothetical treatment plan derived from 68Ga-FAPI will be compared with the conventional treatment already performed, to explore a potential change in patient management.

Nell’obiettivo primario e in quello secondario gli endpoints della performance degli esami PET/TC con 68Ga-FAPI verranno categorizzati come positivi o negativi, sulla base della valutazione indipendente di almeno due medici nucleari esperti in imaging oncologico. In caso di discordanza tra i due lettori o di riscontro di reperti non conclusivi, verrà raggiunto un consenso sulla base dell’opinione di un terzo medico nucleare esperto, anch’esso indipendente.
I reperti verranno valutati dai medici nucleari come positivi per captazione di 68Ga-FAPI se il SUVmax del radiofarmaco in una VOI specifica che include interamente la lesione è > del SUVmean del background (tessuti circostanti) che verrà calcolato in una VOI di 1 cm.
I reperti verranno giudicati dai medici nucleari negativi per captazione di 68Ga-FAPI se non presenteranno captazione del radiofarmaco ovvero una captazione inferiore al background circostante (SUVmax reperto dubbio/SUVmean del background =1.
I risultati dell’indagine PET/TC con 68Ga-FAPI verranno valutati dai medici nucleari come VP/FP/VN/FN sulla base del risultato dell’esame istologico, quando disponibile; altrimenti sulla base del confronto con le indagini di stadiazione convenzionale (TC e PET/TC con 18F-FDG) e con il follow up clinico-strumentale nei 12 mesi successivi all’indagine sperimentale.
Verranno calcolate sensibilità, specificità, accuratezza, PPV e NPV, su un'analisi per paziente e per regione, per valutare la performance della PET/TC con 68Ga-FAPI.
L’accuratezza della PET/TC con 68Ga-FAPI verrà calcolata con la seguente formula statistica:
(VERI POSITIVI+VERI NEGATIVI)/TOTALE PAZIENTI
La sensibilità della PET/TC con 68Ga-FAPI verrà calcolata con la seguente formula statistica:
VERI POSITIVI/(VERI POSITIVI+FALSI NEGATIVI)
La specificità della PET/TC con 68Ga-FAPI verrà calcolata con la seguente formula statistica:
VERI NEGATIVI/(VERI NEGATIVI+FALSI POSITIVI)
Il valore predittivo negativo della PET/TC con 68Ga-FAPI verrà calcolata con la seguente formula statistica:
VERI NEGATIVI/(VERI NEGATIVI+ FALSI NEGATIVI)
Il valore predittivo positivo della PET/TC con 68Ga-FAPI verrà calcolata con la seguente formula statistica:
VERI POSITIVI/(VERI POSITIVI+FALSI POSITIVI)

La performance delle variabili continue semiquatitative PET (ad esempio SUVmax e TBR) (obiettivo secondario) verrà valutata in relazione al risultato dell’esame istologico, quando disponibile; altrimenti sulla base del confronto con le indagini di stadiazione convenzionale (TC e PET/TC con [18F] FDG) e con il follow up clinico-strumentale nei 12 mesi successivi all’indagine sperimentale.
Nei pazienti non chirurgici verrà calcolato la percentuale di positività (positivity rate) della PET/TC con 68Ga-FAPI e la concordanza con l’imaging di stadiazione convenzionale.
Nei pazienti indirizzati a chirurgia radicale, i risultati della PET/TC (T e N) saranno validati dall’esame istopatologico, eseguito secondo il normale percorso assistenziale, dei campioni chirurgici.
Il follow up clinico-diagnostico, eseguito routinariamente dall’ Unità di chirurgia toracica per almeno 1 anno dopo l'intervento, sarà utilizzato come standard di riferimento per validare i risultati della PET in siti non trattati chirurgicamente.
Al termine dello studio, l'ipotetico piano di trattamento derivato da 68Ga-FAPI sarà confrontato con il trattamento convenzionale già eseguito, per esplorare un potenziale cambiamento nella gestione dei pazienti.

E.5.1.1

Timepoint(s) of evaluation of this end point

Time required for subsequent histological examination, when available, or for clinical outcome (12-month follow-up). It will take 36 months to achieve the overall objectives.

Tempo necessario per il successivo esame istologico, quando disponibile, oppure per l'outcome clinico (follow up di 12 mesi). Per il raggiungimento degli obiettivi complessivi saranno necessari 36 mesi.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Time required for subsequent histological examination, when available, or for clinical outcome (12-month follow-up). It will take 36 months to achieve the overall objectives.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

The trial will end at the end of the 12-month follow-up of the enrolled patients and the evaluation of the hypothetical alternative treatment plan based on the results of the experimental examination compared with the treatment already performed based on conventional staging and related data management and analysis.

La sperimentazione si concluderà al termine del follow up di 12 mesi dei pazienti arruolati e la valutazione dell'ipotetico piano di trattamento alternativo basato sui risultati dell'esame sperimentale a confronto con il trattamento già eseguito basato sulla stadiazione convenzionale e relativi data management e analisi.

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-12-07.

Yes

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)

Standard care pathway

Normale percorso assistenziale

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

2022-03-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-20

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

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