Clinical Trials Register

Summary
EudraCT Number:	2016-002978-13
Sponsor's Protocol Code Number:	Verde_Nano
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

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-002978-13

A.3

Full title of the trial

Assessment of the feasibility and clinical efficacy of the ICG - 99mTc - nanocolloid for sentinel lymph node biopsy

Valutazione della fattibilit¿ ed efficacia clinica del ICG-99mTc-Nanocolloide per la biopsia del linfonodo sentinella

A.3.1

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

Assessment of a novel hybrid radiopharmaceutical¿s use (ICG - 99mTc ¿ nanocolloid) applied in sentinel lymph node biopsy

Valutazione dell¿utilizzo di un nuovo radiofarmaco (ICG-99mTc-Nanocolloide) impiegato nella biopsia del linfonodo sentinella

A.3.2

Name or abbreviated title of the trial where available

Verde_Nano

A.4.1

Sponsor's protocol code number

Verde_Nano

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	AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
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	Associazione Contro il Melanoma ONLUS
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	Societ¿ B.S.N Biological Sales Network srl
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	U.O. medicina Nucleare
B.5.2	Functional name of contact point	U.O. medicina Nucleare
B.5.3	Address:
B.5.3.1	Street Address	Via Roma 67
B.5.3.2	Town/ city	Pisa
B.5.3.3	Post code	56126
B.5.3.4	Country	Italy
B.5.4	Telephone number	050993127
B.5.5	Fax number	0050992124
B.5.6	E-mail	g.manca@med.unipiit

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.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VERDE INDOCIANINA
D.3.9.2	Current sponsor code	VERDE INDOCIANINA
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ALBUMINA UMANA PARTICELLE NANOCOLLOIDALI
D.3.9.2	Current sponsor code	ALBUMINA UMANA PARTICELLE NANOCOLLOIDALI
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	0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIO PERTECNETATO 99mTC
D.3.9.2	Current sponsor code	SODIO PERTECNETATO 99mTC
D.3.10	Strength
D.3.10.1	Concentration unit	mCi/ml millicurie(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0
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)	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

Patients with breast cancer or melanoma candidates for sentinel node biopsy surgery.
The regional lymph nodes are the most common site of metastatic involvement in patients with cutaneous melanoma and breast cancer, before the disease spreads to other organs. The presence / absence of lymph node metastasis has been shown to be the most important way to predict survival and guide therapeutic choices in patients suffering from early- melanoma and breast cancer.

Pazienti con cancro al seno o melanoma candidati ad intervento di biopsia del linfonodo sentinella.
I linfonodi regionali sono la sede pi¿ comune di metastasi nei pazienti con melanoma cutaneo e cancro al seno, prima che la malattia si diffonda ad altri organi. La presenza / assenza di metastasi linfonodali si ¿ dimostrata essere il metodo pi¿ importante per predire la sopravvivenza e guidare le scelte terapeutiche in pazienti affetti da melanoma precoce e cancro al seno.

E.1.1.1

Medical condition in easily understood language

Patients with breast cancer or melanoma candidates for sentinel node biopsy surgery

Pazienti con cancro al seno o melanoma candidati ad intervento di biopsia del linfonodo sentinella

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	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10073554
E.1.2	Term	Sentinel node biopsy
E.1.2	System Organ Class	100000004848

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 primary aim of this experimental study is to verify the clinical efficacy of the radiopharmaceutical 99mTc - ICG ¿ nanocolloid for Sentinel Lymph Node (SNL) biopsy in patients with breast cancer and melanoma, in terms of Identification Rate (IR, defined as the ratio between the number of surgical procedures in which at least one SLN is removed and the number of total surgical procedures performed )

Lo scopo primario del nostro studio sperimentale ¿ quello di verificare l¿efficacia clinica dell¿utilizzo del radiofarmaco ICG-99mTc-nanocolloide per la biopsia del SLN in pazienti affetti da carcinoma mammario e melanoma, in termini di IR (definita come il rapporto tra il n¿ di procedure chirurgiche in cui si asporta almeno un SLN sul n¿ di procedure chirurgiche totali eseguite)

E.2.2

Secondary objectives of the trial

1) Calculation of the relationship between number of SLNs preoperatively displayed with lymphoscintigraphy and number of SLNs intraoperatively removed.
2) Calculation of the fluorescent / radioactive signal ratio for each SLN removed intraoperatively , as an index of the in vivo lymphnode uptake of the radiopharmaceutical .

3) data collection about hybrid radiopharmaceutical's safety assessment after its administered and during the follow-up

1) Calcolo del rapporto tra n¿ di SLNs visualizzati preoperatoriamente con linfoscintigrafia e n¿ di SLNs asportati intraoperatoriamente.
2) Calcolo del rapporto segnale fluorescente/segnale radioattivo per ogni SLN asportato intraoperatoriamente, come indice della captazione linfonodale in vivo del radiofarmaco.
3) Valutazione della sicurezza del radiofarmaco ibrido tramite raccolta di dati, al momento della somministrazione e nella visita di follow-up, su eventuali eventi avversi accorsi

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Breast cancer
Patients will be candidates of both sexes , aged = 18 , diagnosed with CT1 - T2N0M0 adenocarcinoma of the breast undergoing SLN biopsy;
Informed consent must be signed by the patient .
Melanoma
Candidates will also be patients of both sexes , aged = 18 , suffering from cutaneous melanoma undergoing SLN biopsy, with Breslow thickness = 1 mm = 4 mm or Breslow = 1 mm , ulcerated and / or at least with 1 mitosis / mm2;
Informed consent must be signed by the patient .

Carcinoma Mammella
Saranno canditati pazienti di entrambi i sessi, di anni = di 18, con diagnosi di adenocarcinoma della mammella cT1-T2N0M0[31] e candidati ad un intervento di biopsia del linfonodo sentinella
Firma del consenso informato da parte del paziente.

Melanoma
Saranno inoltre candidati pazienti di entrambi i sessi, di anni = di 18, affetti da melanoma cutaneo candidati ad un intervento di biospia del linfonodo sentinella con spessore di Breslow = 1 mm = 4 mm o con Breslow = 1 mm, ulcerato e/o almeno con 1 mitosi/mm2;
Firma del consenso informato da parte del paziente.

E.4

Principal exclusion criteria

1 ) clinically positive lymph nodes 2 ) previous surgery of the breast 3 ) multicentric breast cancer , 4 ) the presence of local infection or inflammatory process in the site of administration of the radiopharmaceutical 5 ) pregnancy and lactation both excluded by anamnestic data collection 6 ) History of previous melanoma or other cancer except basal-cell carcinoma and in situ carcinoma of the uterine cervix 7 ) Inability of the patient to cooperate with the procedure 8 ) known hypersensitivity to products containing human albumin and / or indocyanine green with or excipients used in such drug formulations 9) Concomitant use of drugs that can reduce the absorption ICG : Anticonvulsants, bisulfites, haloperidol, heroin, meperidine, metamizole, methadone, nitrofurantoin, alcaliodi opium, phenobarbital, fenibutazione; Concomitant use of drugs that can increase the absorption ICG : cyclopropane , probenecid , rifamycin

1) linfonodi clinicamente positivi 2) precedenti interventi chirurgici sulla mammella 3) multicentricità della neoplasia mammaria, 4) presenza di infezione locale o franco processo infiammatorio nel sito di somministrazione del radiofarmaco 5) gravidanza ed allattamento entrambe escluse tramite raccolta dati anamnestici 6) anamnesi positiva per pregresso melanoma o altra neoplasia eccetto Ca baso-cellulare e Ca della cervice uterina in situ 7) incapacità del paziente a cooperare con la procedura 8) accertata ipersensibilità ai prodotti contenenti albumina umana e/o verde d’indocianina o agli eccipienti utilizzati in tali formulazioni farmacologiche 9) Concomitante utilizzo di medicinali che posso ridurre l’assorbimento dell’ICG: Anticonvulsivanti, bisolfiti, aloperidolo, eroina,meperidina,metamizolo, metadone, nitrofurantoina, alcaliodi dell’oppio, fenobarbital, fenibutazione; Concomitante utilizzo di medicinali che posso aumentare l’assorbimento dell’ICG: ciclopropano, probenecid, rifamicina

E.5 End points

E.5.1

Primary end point(s)

Identification rate of the method ( defined as the ratio between the n ° of surgical procedures that removes at least one SLN on the number of total surgical procedures performed ) .

“Identification rate” della metodica (definita come il rapporto tra il n° di procedure chirurgiche in cui si asporta almeno un linfonodo sentinella sul n° di procedure chirurgiche totali eseguite).

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint will be assessed during surgical time

L'endpoint primario sarà valutato nel corso dell'asportazione chirurgica dei linfonodi

E.5.2

Secondary end point(s)

1) Calculation of the relationship between n¿ of SLNs displayed by preoperative lymphoscintigraphy and n ¿ of SLNs intraoperatively removed .

2)Calculation of the fluorescent / radioactive signal ratio for each " sentinel node " removed intraoperatively and comparison with the reference value of the hybrid radiopharmaceutical .
3) Recording of any adverse events to the hybrid radiopharmaceutical at the time of administration (during lymphscintigraphy) or late (in the follow - up visit)

1) Calcolo del rapporto tra n¿ di ¿linfonodi sentinella¿ visualizzati preoperatoriamente con linfoscintigrafia e n¿ di ¿linfonodi sentinella¿ asportati intraoperatoriamente.
2) Calcolo del rapporto segnale fluorescente/segnale radioattivo per ogni ¿linfonodo sentinella¿ asportato intraoperatoriamente e confronto con il valore di riferimento del radiofarmaco ibrido.
3) Registrazione di eventuali eventi avversi al radiofarmaco ibrido accorsi al momento della somministrazione (durante la linfoscitigrafia) o tardivamente (nella visita di follow-up).

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoint 1 ) and 2 ) will be evaluated immediately after lymph nodes' surgical removal

The endpoint Secondary 3 ) will be evaluated both during lymphoscintigraphy and in follow -up visit

Gli endpoint secondari 1) e2) saranno valutati durante e immediatamente dopo l'asportazione chirurgica dei linfonodi
L'endpont secondario 3) sar¿ valutato sia durante la precedura linfoscintigrafica che nella visita di follow-up.

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)

Yes

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.8.5.1

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

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 be followed as routine

I pazienti saranno seguiti come di routine

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

2016-09-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-07-21

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

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