Clinical Trials Register

Summary
EudraCT Number:	2019-000793-27
Sponsor's Protocol Code Number:	IRST100.42
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2021-05-24
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

2019-000793-27

A.3

Full title of the trial

A phase II study on adjuvant Vaccination with dendritic cells loaded with autologous tumor homogenate in resected stage IV rare cancers: Head&Neck (H&N), neuroendocrine Tumors (NET) and soft tissue sarcoma (STS).

Studio di fase II di vaccinazione a scopo adiuvante con cellule dendritiche caricate con omogenato tumorale autologo dopo chirurgia radicale in pazienti affetti da tumori del distretto testa/collo (H&N), tumori neuroendocrini (NET) e sarcomi dei tessuti molli in stadio IV (STS).

A.3.1

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

A phase II study on adjuvant Vaccination with dendritic cells in resected stage IV rare cancers: Head&Neck (H&N), neuroendocrine Tumors (NET) and soft tissue sarcoma (STS).

Studio di fase II di vaccinazione a scopo adiuvante con cellule dendritiche dopo chirurgia radicale in pazienti affetti da tumori del distretto testa/collo (H&N), tumori neuroendocrini (NET) e sarcomi dei tessuti molli in stadio IV (STS).

A.3.2

Name or abbreviated title of the trial where available

RaC-Ad

A.4.1

Sponsor's protocol code number

IRST100.42

A.5.4

Other Identifiers

Name:

Number:

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 SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI (IRST) S.R.L. IRCCS
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	IRST IRCCS
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	IRST IRCCS
B.5.2	Functional name of contact point	Centro di Coordinamento Studi IRST
B.5.3	Address:
B.5.3.1	Street Address	Dipartimento di Oncologia ed Ematologia, Ospedale Civile S. Maria delle Croci, viale Randi, 5
B.5.3.2	Town/ city	Ravenna
B.5.3.3	Post code	48121
B.5.3.4	Country	Italy
B.5.4	Telephone number	0547394547
B.5.5	Fax number	0544285330
B.5.6	E-mail	cc.ubsc@irst.emr.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.2.1.2	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	IL2_IRSTIRCCS
D.3.2	Product code	[IL2_IRSTIRCCS]
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	00705500
D.3.9.1	CAS number	110942-02-4
D.3.9.2	Current sponsor code	IL2_IRSTIRCCS
D.3.9.4	EV Substance Code	SUB169687
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3000000
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	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)	Yes
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	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	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	DC-VACCINE_IRSTIRCCS
D.3.2	Product code	[DC-VACCINE_IRSTIRCCS]
D.3.4	Pharmaceutical form	Suspension 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	DC-VACCINE_IRSTIRCCS
D.3.9.2	Current sponsor code	DC-VACCINE_IRSTIRCCS
D.3.9.4	EV Substance Code	SUB169507
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	7000000 to 14000000
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)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	Yes
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)	Yes
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

Resected stage IV rare cancers: Head&Neck (H&N), neuroendocrine tumors (NET) and soft tissue sarcoma (STS).

Tumori rari di stadio IV resecati: testa/collo (H&N), tumori neuroendocrini (NET) e sarcomi dei tessuti molli (STS).

E.1.1.1

Medical condition in easily understood language

Rare cancers: Head&Neck (H&N), neuroendocrine tumors (NET) and soft tissue sarcoma (STS).

Tumori rari: testa/collo (H&N), tumori neuroendocrini (NET) e sarcomi dei tessuti molli (STS).

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10071536
E.1.2	Term	Head and neck cancer stage IV
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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10062476
E.1.2	Term	Neuroendocrine tumor
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	10068771
E.1.2	Term	Soft tissue neoplasm
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

Safety; co-primary objective: immunological efficacy

Sicurezza; obiettivo co-primario: efficacia immunologica

E.2.2

Secondary objectives of the trial

- To evaluate clinical outcome of the patients: overall survival and relapse-free survival
- To evaluate the predictive role of a positive DTH test after at least three vaccine administrations.
- immunological objectives:
1) To evaluate the prognostic or predictive role of the presence and/or development of a specific cell-mediated immune response for a panel of known tumour antigens.
2) To evaluate the persistence of an antitumor immune response after the completion of the vaccination program both in relapsed and in disease-free patients.
3) To evaluate the serum level of a panel of pro-inflammatory/pro-angiogenic factors.
4) To evaluate the predictive role of immune cells in the peripheral blood and in the tumour microenvironment (TME).
5) To evaluate the predictive role of tumour antigen expression in tumour tissue.

- Esito clinico: sopravvivenza globale e sopravvivenza libera da recidive
- Valutazione del ruolo predittivo del test DTH positivo dopo almeno tre somministrazioni di vaccino
- Obiettivi immunologici:
1) Valutare il ruolo prognostico o predittivo della presenza e/o lo sviluppo di una specifica risposta immunitaria cellulo-mediata per un gruppo di antigeni tumorali noti.
2) Valutare la persistenza di una risposta immunitaria antitumorale dopo il completamento del programma di vaccinazione sia in pazienti recidivanti che in pazienti senza malattia.
3) Valutare il livello sierico di un panel di fattori pro-infiammatori/pro-angiogenetici.
4) Valutare il ruolo predittivo delle cellule immunitarie nel sangue periferico e nel microambiente tumorale (TME).
5) Valutare il ruolo predittivo dell'espressione degli antigeni tumorali nel tessuto tumorale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Histologically confirmed stage IV rare cancers: Head&Neck Squamous Cell Carcinoma (HNSCC), Neuroendocrine Tumors (NET) and Soft Tissue Sarcoma (STS), surgically treated with radical intent.
• The autologous surgical specimen must have been collected and sent to the Somatic Cell Therapy Lab of IRST IRCCS and must fulfil all the acceptance criteria prescribed by the GMP procedures.
• The patient must be disease-free, candidates for only observation as per clinical practice (no standard treatment is available after surgery).
• Age >=18 years.
• ECOG performance status 0 or 1.
• Acceptable organ function.

• Tumori rari, stadio IV, conferma istologica di carcinoma a cellule squamose di testa e collo (HNSCC) (H & N) o tumore neuroendocrino (NET) o sarcoma dei tessuti molli (STS). Neoplasia trattata chirurgicamente con intento radicale.
• Disponibilità di un campione di tessuto tumorale autologo ottenuto dall’intervento chirurgico, che deve essere stato raccolto e inviato al Laboratorio di terapia Cellulare Somatica (TCS) dell’IRST IRCCS e che deve soddisfare tutti i criteri di accettazione prescritti dalle procedure GMP.
• paziente libero da malattia, candidato alla sola osservazione per pratica clinica (non sono disponibili alternative terapeutiche dopo chirurgia).
• Età = 18 anni.
• PS ECOG=0 o 1.
• Funzionalità d’organo accettabili.

E.4

Principal exclusion criteria

• Patients with residual disease after surgery. Marginal resection of any lesion in the absence of clinically evident residual disease is acceptable.
• Patient who completed surgery more than 90 days before study enrolment.

• Pazienti con malattia residua dopo l'intervento chirurgico. La resezione marginale di qualsiasi lesione in assenza di malattia residua clinicamente evidente è accettabile.
• Intervento chirurgico eseguito oltre i 90 giorni precedenti l’inserimento del paziente in studio

E.5 End points

E.5.1

Primary end point(s)

Safety, measured as proportion of patients experienced grade 3 or higher adverse events; co-primary endpoint: immunological efficacy, expressed as the number of patients who show enhancement of the proportion of circulating immune effectors specific for a selected panel of associated antigens for each disease

Sicurezza, misurata come proporzione di pazienti con eventi avversi di grado 3 o superiore; endpoint co-primario: efficacia immunologica, espressa come numero di pazienti che mostrano un aumento della proporzione di effettori immunitari circolanti specifici per un gruppo selezionato di antigeni associati per ciascuna malattia

E.5.1.1

Timepoint(s) of evaluation of this end point

7 years

7 anni

E.5.2

Secondary end point(s)

Clinical outcome: Overal Survival and Relapse Free Survival; Evaluation of the predictive role of a positive DTH test after at least three vaccine administrations; Immunological endpoints:
1) The definition of the prognostic or predictive role of the presence and/or development of a specific cell-mediated immune responses determined by IFNgamma ELISPOT.; Immunological endpoints:
2) To evaluate the persistence of an antitumor immune response after the completion of the vaccination program both in relapsed and in disease-free patients, assessed by IFNgamma ELISPOT assay.; Immunological endpoints:
3) To evaluate the serum level of a panel of pro-inflammatory/pro-angiogenic factors (such as IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFalpha, VEGF and Fibronectin) by cytometric bead array.; Immunological endpoints:
4) To evaluate the predictive role of immune cells in the peripheral blood and in the tumour microenvironment (TME). To this aim functional phenotyping of circulating and in situ immune effectors/regulators will be conducted.; Immunological endpoints:
5) To evaluate the predictive role of tumour antigen expression in tumour tissue. IHC analyses will be conducted on FFPE samples to evaluate the expression of TAAs (such as NY-ESO, PRAME, MAGE-A1).

Esito clinico: sopravvivenza globale e sopravvivenza libera da recidive; Valutazione del ruolo predittivo del test DTH positivo dopo almeno tre somministrazioni di vaccino; Endpoints immunologici:
1) Valutare il ruolo prognostico o predittivo della presenza e/o lo sviluppo di una specifica risposta immunitaria cellulo-mediata per un gruppo di antigeni tumorali noti, determinato tramite IFNgamma ELISPOT; Endpoints immunologici:
2) Valutare la persistenza di una risposta immunitaria antitumorale dopo il completamento del programma di vaccinazione sia in pazienti recidivanti che in pazienti senza malattia, attraverso il test IFNgamma ELISPOT.; Endpoints immunologici:
3) Valutare il livello sierico di un panel di fattori pro-infiammatori/pro-angiogenetici (come IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNFalpha, VEGF e Fibronectina) mediante citometria (cytometric bead array).; Endpoints immunologici:
4) Valutare il ruolo predittivo delle cellule immunitarie nel sangue periferico e nel microambiente tumorale (TME). A tal fine sarà condotta la fenotipizzazione funzionale degli effettori / regolatori immuni circolanti e in situ.; Endpoints immunologici:
5) Valutare il ruolo predittivo dell'espressione degli antigeni tumorali nel tessuto tumorale. Saranno condotte analisi di immunoistochimica su campioni FFPE per valutare l'espressione di TAA (come NY-ESO, PRAME, MAGE-A1).

E.5.2.1

Timepoint(s) of evaluation of this end point

7 years; 7 years; 7 Years; 7 years; 7 years; 7 years; 7 years

7 anni; 7 anni; 7 anni; 7 anni; 7 anni; 7 anni; 7 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

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

Yes

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)

After treatment phase, each patient will perform periodic follow-up visits (with clinical, laboratory and instrumental assays) every 4 months, until disease relapse (subsequently no further visits or examinations are scheduled, only six-monthly contacts to evaluate the survival), for a total follow-up period of 5 years.

Dopo la fase di trattamento ciascun paziente eseguirà visite periodiche di follow-up (con controlli clinici, laboratoristici e strumentali) ogni 4 mesi, fino ad eventuale ripresa di malattia (successivamente non si prevedono ulteriori visite o esami, ma solo contatti semestrali per valutare la sopravvivenza), per un periodo totale di follow-up di 5 anni.

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

2019-09-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-10-23

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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