Clinical Trials Register

Summary
EudraCT Number:	2020-002548-21
Sponsor's Protocol Code Number:	ProgettoAIRCId.21939
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:	2020-10-22
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

2020-002548-21

A.3

Full title of the trial

Personalized therapy of metastatic thyroid cancer: biological characterization and optimization with 124I PET dosimetry

Terapia personalizzata per il trattamento del carcinoma tiroideo metastatico: caratterizzazione biologica e ottimizzazione mediante dosimetria con 124I PET

A.3.1

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

Personalized therapy of metastatic thyroid cancer: biological characterization and optimization with 124I PET dosimetry

Terapia personalizzata per il trattamento del carcinoma tiroideo metastatico: caratterizzazione biologica e ottimizzazione mediante dosimetria con 124I PET

A.3.2

Name or abbreviated title of the trial where available

Progetto AIRC Id. 21939

A.4.1

Sponsor's protocol code number

ProgettoAIRCId.21939

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN00000000

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00000000

A.5.3

WHO Universal Trial Reference Number (UTRN)

U0000-0000-0000

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	FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
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	AIRC
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 nazionale dei Tumori
B.5.2	Functional name of contact point	Clinical Trial Center
B.5.3	Address:
B.5.3.1	Street Address	Via Venezian 1
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	+390223903063
B.5.5	Fax number	+390223903991
B.5.6	E-mail	trialcenter@istitutotumori.mi.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.2.1.1.1	Trade name	Ioduro 124 Sodico
D.2.1.1.2	Name of the Marketing Authorisation holder	NA
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	Ioduro 124 sodico
D.3.2	Product code	[124INaI]
D.3.4	Pharmaceutical form	Concentrate for solution for 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	SODIO IODURO
D.3.9.2	Current sponsor code	Ioduro 124 sodico
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	172
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.IMP: 2
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	SODIO IODIDE [131-I]GE HEALTHCARE - 74 MBQ/ML SOLUZIONE INIETTABILE 1 FLACONCINO DA 10 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	GE HEALTHCARE S.R.L.
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	Sodio Ioduro (131I)
D.3.2	Product code	[Sodio Ioduro (131I)]
D.3.4	Pharmaceutical form	Concentrate for 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	SODIO IODURO 131I
D.3.9.2	Current sponsor code	Sodio Ioduro (131I)
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	74
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIO IODURO 131I
D.3.9.2	Current sponsor code	Sodio Ioduro (131I)
D.3.10	Strength
D.3.10.1	Concentration unit	MBq/ml megabecquerel(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	925
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

metastatic thyroid cancer

carcinoma tiroideo metastatico

E.1.1.1

Medical condition in easily understood language

metastatic thyroid cancer

carcinoma tiroideo metastatico

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	10076603
E.1.2	Term	Poorly differentiated thyroid 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

The present study aims to optimize the nuclear medicine therapeutic approach (radioiodine treatment) to metastatic DTC and to deepen the knowledge on 131I inefficacy.
Lesion dosimetry and biological characterization are necessary for both purposes. We therefore propose a twofold path:
• to investigate if dosimetry-based 131I administration may increase efficacy as compared to that obtained with fixed activity, with an acceptable toxicity in DTC patients with soft tissue and skeletal metastasis
• to study if the mutational status, the gene expression and the variations of miRNA profiles before and after therapy of DTCs may be related to lesions’ refractoriness, even to personalized, 131I therapy

Il presente studio mira ad ottimizzare e personalizzare la terapia medico-nucleare con radioiodio (131I), nonché ad approfondire le conoscenze sulla possibile inefficacia del trattamento.
Proponiamo, quindi, un duplice obiettivo:
• indagare se la somministrazione personalizzata di 131I basata sulla dosimetria possa aumentare l'efficacia terapeutica;
• studiare se lo stato mutazionale, l'espressione genica e le variazioni dei profili di microRNA, prima e dopo la terapia con DTC, possano essere correlate alla refrattarietà delle lesioni, anche a seguito di terapia con 131I personalizzata

E.2.2

Secondary objectives of the trial

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

Pharmacogenetics
Version: v.1.0
Date: 22/06/2020
Title: GENE AND miRNA EVALUATION
Objectives: to identify molecular elements influencing iodine and 18F-FDG uptakes

Farmacogenetica
Versione: v.1.0
Data: 22/06/2020
Titolo: Profili Trascrittomici: Espressione Genetica e microRNA
Obiettivi: identificare i profili trascrittomici del DTC iodio-resistente

E.3

Principal inclusion criteria

• Histo-pathological diagnosis of DTC
• At least one documented non surgically-curable soft-tissue metastasis previously untreated
• ECOG performance status = 0 - 1
• Age = 18 years old
• Life expectancy > 6 months
• Females of childbearing age must have negative serum pregnancy test prior to registration and agree to use birth control throughout the study and for 6 months after completion
of therapy
• Preserved hematologic and renal function (hemoglobin > 10 g/dL; WBC > 3500/uL; neutrophilis > 50%; PLT > 100000/uL; albumin = 2.5 g/dL; creatinine = 2 mg/dL)
• Signed informed consent

• Diagnosi isto-patologica di DTC
• La presenza di almeno una metastasi documentata ai tessuti molli, non curabile chirurgicamente e non trattata precedentemente
• Performance Status ECOG 0 - 1
• Età = 18 anni
• Aspettativa di vita > 6 mesi
• Le donne in età fertile devono essere sottoposte a test di gravidanza sierico che deve risultare negativo prima della registrazione nella visita di pre-screening (figura 1) e devono
accettare la contraccezione durante lo studio e per i 6 mesi dopo il completamento della terapia
• Funzionalità renale ed ematologica: emoglobina > 10 g/dL; WBC > 3500/uL; neutrofili > 50%; PLT > 100000/uL; albumina = 2.5 g/dL; creatinina = 2 mg/dL
• Firma del consenso informato

E.4

Principal exclusion criteria

• All lesions surgically resectable
• Minimal lymph nodal disease (diameter < 1 cm, up to 2 nodes)
• Patient with skeletal metastases only
• Lung diffuse miliary micro-metastases (cannot be assessed according to RECIST criteria; severe lung toxicity may be expected after high activity administration)
• Ongoing pregnancy (enrollment could be considered after delivery)
• Breast-feeding (enrollment could be considered after suspension)
• Refusal of male and female patients to use an effective contraception method during the study and for 6 months after completion of protocol therapy
• Impossibility to undergo follow-up procedures
• Presence of medical, psychiatric or surgical condition, not adequately controlled by treatment, which would likely affect subjects’ ability to complete the protocol
• Assumption of any anti-tumor therapy including chemotherapy, biological or investigational drug treatments
• Assumption of any myelotoxic drugs
• Any other oncologic disease that required treatment in the last 5 years.

• Lesioni tutte chirurgicamente resecabili
• Malattia linfonodale minima (diametro <1 cm, fino a 2 noduli)
• Paziente con sole metastasi scheletriche
• Micro-metastasi miliariformi diffuse a livello polmonare
• Gravidanza in corso (l'inclusione potrebbe essere presa in considerazione dopo il parto)
• Rifiuto dei pazienti (sia uomini che donne) all’utilizzo di un metodo contraccettivo efficace durante lo studio e fino a 6 mesi dopo il completamento della terapia
• Impossibilità a sottoporsi a procedure di follow-up
• Presenza di condizioni mediche, psichiche o chirurgiche non adeguatamente controllate, che potrebbero influenzare la capacità dei soggetti di completare il protocollo
• Assunzione di qualsiasi terapia antitumorale
• Assunzione di eventuali farmaci mielotossici
• Qualsiasi altra malattia oncologica che ha richiesto il trattamento negli ultimi 5 anni.

E.5 End points

E.5.1

Primary end point(s)

Evaluation of complete response (CR) rate on soft tissue metastases to radioiodine therapy optimized with personalized pre-treatment dosimetry based on 124I-PET/CT. The best response will be considered.

Valutazione del rateo di risposta completa (CR) sulle metastasi dei tessuti molli dopo terapia con radioiodio, ottimizzata e personalizzata grazie a dosimetria pretrattamento con 124I-PET/CT. Verrà considerata la migliore risposta nel tempo.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 years

4 anni

E.5.2

Secondary end point(s)

Assessment of:
• acute toxicity rate and severity
• the association among pre-treatment glucose metabolism, 124I uptake and therapy response
• the association among genetic mutations on cancer tissue, pre- and post-treatment miRNA expression, pre- and post-treatment glucose metabolism, iodine uptake, and 131I therapy response

Valutazione:
• dell’incidenza e del grado di tossicità acuta
• dell’associazione tra metabolismo del glucosio pretrattamento, captazione di 124I e risposta terapeutica
• dell'associazione tra mutazioni genetiche sul tessuto canceroso, espressione di microRNA pre- e post-trattamento, metabolismo del glucosio pre- e post-trattamento, assorbimento di iodio e risposta alla terapia con 131I

E.5.2.1

Timepoint(s) of evaluation of this end point

4 years

4 anni

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

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

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.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 undergo a 6-month follow-up

I pazienti saranno sottoposti ad un follow-up di 6 mesi

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

2021-01-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-28

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