Clinical Trials Register

Summary
EudraCT Number:	2015-000894-11
Sponsor's Protocol Code Number:	IRST153.04
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:	2017-12-20
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

2015-000894-11

A.3

Full title of the trial

Vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer: a phase II study

Vaccinazione complementare con cellule dendritiche autologhe caricate con omogenato tumorale autologo dopo chirurgia radicale per carcinoma del colon o retto metastatico: studio di fase II.

A.3.1

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

Vaccination with autologous dendritic cells loaded with autologous tumour homogenate after curative resection for stage IV colorectal cancer: a phase II study

Vaccinazione complementare con cellule dendritiche autologhe caricate con omogenato tumorale autologo dopo chirurgia radicale per carcinoma del colon o retto metastatico: studio di fase II.

A.3.2

Name or abbreviated title of the trial where available

COREVAX-1

A.4.1

Sponsor's protocol code number

IRST153.04

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	+390544285813
B.5.5	Fax number	+390544285330
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	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.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5000000
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.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	PROLEUKIN - 18.000.000 UI POLVERE PER SOLUZIONE INIETTABILE O PER INFUSIONE 10 FLACONCINI IN VETRO DA 22.000.000 UI
D.2.1.1.2	Name of the Marketing Authorisation holder	NOVARTIS FARMA S.P.A.
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.3.4	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	INTERLEUCHINA-2 UMANA RICOMBINANTE
D.3.9.1	CAS number	110942-02-4
D.3.9.2	Current sponsor code	IL2_IRSTIRCCS
D.3.9.3	Other descriptive name	INTERLEUCHINA-2 UMANA RICOMBINANTE
D.3.9.4	EV Substance Code	SUB05303MIG
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.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

colorectal cancer

tumore del colon-retto

E.1.1.1

Medical condition in easily understood language

colorectal cancer

tumore del colon-retto

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	10038029
E.1.2	Term	Rectal adenocarcinoma stage IV
E.1.2	System Organ Class	100000004864

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	10001172
E.1.2	Term	Adenocarcinoma of colon stage IV
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

1) safety 2) Immunological efficacy, expressed as number of patients who show enhancement of the proportion of circulating immune effectors specific for a selected panel of CRC-associated antigens.

1) Sicurezza 2) Efficacia immunologica, espressa come numero di pazienti che mostrano miglioramento nella proporzione di effettori immunologici circolanti specifici per un selezionato pannello di antigeni CRC-associati.

E.2.2

Secondary objectives of the trial

1) Clinical outcome of the patients (OS, RFS, TTR). 2) To evaluate the predictive role of the development of a positive DTH test after at least three vaccine administrations. 3) To evaluate the persistence of an antitumor immune response after the completion of the vaccination program. 4) To evaluate the prognostic or predictive role of the enhancement of a specific immune response. 5) To evaluate a panel of inflammatory cytokines involved in antitumor immune response. 6) To evaluate the predictive role of immune cells in tumour microenvironment. 7) To evaluate the predictive role of tumour antigen expression.

1) Esito clinico dei pazienti (Sopravvivenza globale (OS), Sopravvivenza libera da ripresa di malattia (RFS), Tempo alla progressione (TTR)). 2) Valutazione del ruolo predittivo dello sviluppo di un test DTH positivo dopo almeno tre somministrazioni di vaccino. 3) Valutazione della persistenza della risposta immunitaria antitumorale dopo il completamento del programma di vaccinazione. 4) Valutazione del ruolo prognostico o predittivo dello sviluppo di una risposta immunitaria specifica. 5) Valutazione di un pannello di citochine infiammatorie coinvolte nella risposta immunitaria antitumorale. 6) Valutazione del ruolo predittivo delle cellule immunitarie nel microambiente tumorale. 7) Valutazione del ruolo predittivo dell’espressione antigenica tumorale.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Histologically confirmed stage IV colorectal cancer 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. - Age >18 years. - ECOG performance status 0 or 1. - Acceptable organ function.

- carcinoma colorettale di stadio IV confermato istologicamente, trattato chirurgicamente con intento radicale. - Il campione chirurgico autologo deve essere stato raccolto e inviato al Laboratorio di Terapia Cellulare Somatica IRST IRCCS e deve soddisfare tutti i criteri di accettazione previsti dalle procedure GMP. - Il paziente deve essere libero da malattia. - Età > 18 anni. - ECOG performance status 0 o 1. - Accettabile funzione d’organo.

E.4

Principal exclusion criteria

- Residual disease after surgery. - Relapse within 6 months since primary treatment of stage I-III colorectal cancer. - Surgery more than 60 days before study enrolment. - History of other neoplastic diseases. - History of congenital or acquired immunodeficiency. - Any positivity for the serologic markers of HBV (including at least anti-HBs antibodies and anti-HBc antibodies), HCV, HIV or Treponema pallidum. - Pregnancy or nursing. - Patients undergone surgery after preoperatory chemotherapy with a fluoropyrimidine plus oxaliplatin, unless they are not candidate for postoperatory chemotherapy with the same schedule in the opinion of the Investigator (e.g. for unacceptable toxicity) or refuse completion of the perioperatory treatment. - Participation in another clinical trial. - Any active inflammatory or autoimmune disease. - Any contraindication to leukaphaeresis.

- Malattia residua dopo l'intervento chirurgico. - Ripresa di malattia entro 6 mesi dal trattamento primario di fase I-III del cancro del colon-retto. - Intervento chirurgico più di 60 giorni prima dell'arruolamento nello studio. - Storia di altre malattie neoplastiche. - Storia di immunodeficienza congenita o acquisita. - Qualsiasi positività per i marcatori sierologici di HBV (inclusi almeno anticorpi anti-HBs e anticorpi anti-HBc), HCV, HIV o Treponema pallidum. - Gravidanza o allattamento. - Pazienti che hanno eseguito terapia preoperatoria con una fluoropirimidina + oxaliplatino seguita da chirurgia e candidabili a successivo completamento con il medesimo trattamento. I pazienti non candidabili alla chemioterapia postoperatoria con lo stesso schema a giudizio del ricercatore (ad esempio per tossicità inaccettabile) o che rifiutino il completamento del trattamento perioperatorio sono eleggibili. - Partecipazione ad un altro studio clinico. - Qualsiasi malattia attiva di tipo infiammatorio o autoimmune. - Qualsiasi controindicazione alla leucaferesi.

E.5 End points

E.5.1

Primary end point(s)

1) Safety 2) Immunological efficacy, expressed as number of patients who show enhancement of the proportion of circulating immune effectors specific for a selected panel of CRC-associated antigens.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 months

30 mesi

E.5.2

Secondary end point(s)

Clinical outcome of the patients (OS, RFS, TTR).
To evaluate the predictive role of the development of a positive DTH test after at least three vaccine administrations.
To evaluate the persistence of an antitumor immune response after the completion of the vaccination program.
To evaluate the prognostic or predictive role of the enhancement of a specific immune response.
To evaluate a panel of inflammatory cytokines involved in antitumor immune response.
To evaluate the predictive role of immune cells in tumour microenvironment.
To evaluate the predictive role of tumour antigen expression.

Esito clinico dei pazienti (Sopravvivenza globale (OS), Sopravvivenza libera da ripresa di malattia (RFS), Tempo alla progressione (TTR)).
Valutazione del ruolo predittivo dello sviluppo di un test DTH positivo dopo almeno tre somministrazioni di vaccino.
Valutazione della persistenza della risposta immunitaria antitumorale dopo il completamento del programma di vaccinazione.
Valutazione del ruolo prognostico o predittivo dello sviluppo di una risposta immunitaria specifica.
Valutazione di un pannello di citochine infiammatorie coinvolte nella risposta immunitaria antitumorale.
Valutazione del ruolo predittivo delle cellule immunitarie nel microambiente tumorale.
Valutazione del ruolo predittivo dell’espressione antigenica tumorale.

E.5.2.1

Timepoint(s) of evaluation of this end point

7 years
30 months
30 months
7 years
30 months
7 years
7 years

7 anni
30 mesi
30 mesi
7 anni
30 mesi
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

Yes

E.6.13.1

Other scope of the trial description

Immunological evaluations (see study objectives)

Valutazioni immunologiche (vedere obiettivi dello studio)

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

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

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

Number of subjects for this age range:

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

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

Yes

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)

The follow-up phase starts after the end of treatment visit and lasts until evidence of disease relapse, study termination, patient lost to follow-up, or withdrawal of the informed consent by the patient. In any case the follow-up phase will end after five years from the completion of study treatment. The evaluations should be performed every four months

La fase di follow-up inizia dopo la visita di fine trattamento e dura fino alla comparsa di recidiva della malattia, oppure al termine dello studio, alla perdita del paziente al follow-up, o alla revoca del consenso. In ogni caso la fase di follow-up si concluderà dopo cinque anni dal completamento del trattamento dello studio. Le valutazioni dovrebbero essere effettuate ogni quattro 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

2016-03-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-13

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

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