Clinical Trials Register

Summary
EudraCT Number:	2019-001641-40
Sponsor's Protocol Code Number:	ESR-17-12933
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
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

2019-001641-40

A.3

Full title of the trial

Induction Durvalumab (MEDI4736) & Radiotherapy (RT) for
Locally Advanced but Resectable Head and Neck Squamous Cell Carcinomas: A Pilot Study

Studio pilota di induzione con Durvalumab (MEDI4736) e Radioterapia (RT) per carcinoma squamoso localmente avanzato ma resecabile del distretto cervicocefalico

A.3.1

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

Study of advacned resectable head and neck cancer with immunotherapy and radiotherapy before surgery

Studio sul trattamento del tumore della testa/collo avanzato ma operabile con immunoterapia e radioterapia prima della chirurgia

A.3.2

Name or abbreviated title of the trial where available

ESR-17-12933

A.4.1

Sponsor's protocol code number

ESR-17-12933

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	ISTITUTI FISIOTERAPICI OSPITALIERI
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	Astra Zeneca
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	Istituti Fisioterapici Ospitalieri
B.5.2	Functional name of contact point	Clinical Trial Center
B.5.3	Address:
B.5.3.1	Street Address	via Elio Chianesi 53
B.5.3.2	Town/ city	Roma
B.5.3.3	Post code	00144
B.5.3.4	Country	Italy
B.5.4	Telephone number	0652666125
B.5.5	Fax number	0652665664
B.5.6	E-mail	filomena.spasiano@ifo.gov.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.2.1.1.1	Trade name	Imfinzi
D.2.1.1.2	Name of the Marketing Authorisation holder	Astra Zeneca
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	IMFINZI
D.3.2	Product code	[DURVALUMAB]
D.3.4	Pharmaceutical form	Lyophilisate 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.3.9.1	CAS number	1428935-60-7
D.3.9.2	Current sponsor code	MEDI 4736
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	50
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	No
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

Advanced resectable head and neck tumor

Tumore della testa/collo avanzato ma resecabile

E.1.1.1

Medical condition in easily understood language

Resectable head and neck cancer

Tumore della testa e del collo operabile

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	10067821
E.1.2	Term	Head and neck cancer
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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10067821
E.1.2	Term	Head and neck cancer
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

To determine the extent by which the administration of neoadjuvant Durvalumab plus fractionated radiotherapy modulates immunobiomarkers, such as T- cell activation, serum cytokines in peripheral blood as well as tumor pathological response and T-cell infiltration in the tumor and to confirm the safety of CBIT as a single agent in combination with RT.

Determinare fino a che punto la somministrazione neoadiuvante di Durvalumab in associazione a RT frazionata modula imarkers immunologici come ad esempio l’attivazione e l’infiltrazione delle cellule T nella sede del tumore sia a livello locale sia linfonodale (effetto cd. abscopale), le citochine seriche, nonché la risposta patologica della malattia.

E.2.2

Secondary objectives of the trial

1. Local and regional activity of neoadjuvant Durvalumab/RT at clinical/radiological (morphologicalandfunctional) examination before surgery.
2. Safety of combination in terms of surgery
3. Feasibility of adjuvant radiotherapy + chemotherapy after surgery

1. Attività del trattamento neoadiuvante a livello clinico e radiologico sia morfologico sia funzionale;
2. Tollerabilità della combinazione in termini di effetti indesiderati all’intervento chirurgico;
3. Fattibilità del trattamento adiuvante post-chirurgico.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Newlydiagnosed,histologicallyconfirmedsquamouscellcarcinomaoftheoralcavity,pharynxand larynx;
• Selected UICC stage IV disease limited to T1-3N2-3 or T4N1-3disease;
• No distant metastases (M0)
• Lesions (both primary and nodal) must be considered amenable of complete surgicalresection;
• Patient must be cleared for surgery (medicallyoperable);
• Age >18 yrs and < 80yrs;
• Eastern cooperative oncology group (ECOG) performance status of 0 or1.
• Body weight>30kg

• Carcinoma squamoso del cavo orale, laringe o faringe in prima diagnosi;
• Stadio UICC IV limitatamente a T1-3N2-3 o T4N1-3;
• No metastasi a distanza (M0)
• La malattia (sia sul T sia su N) deve essere considerata resecabile in modo oncologicamente radicale;
• Il paziente deve potere essere sottoposto a chirurgia (medicalmente operabile);
• Età >18 aae < 80 aa;
• Eastern cooperative oncology group (ECOG) performance status di 0 o1.
• Peso corporeo superiore a 30kg

E.4

Principal exclusion criteria

• cN0 disease even if stage IV;
• Definitive clinical or radiologic evidence of distant metastatic disease(M1);
• Carcinoma of the head and neck of unknown primary site origin or lack of a visible primarysite;
• Prior head neck regionirradiation;
• Synchronous primarycancers;
• Any other previous malignancy within 5years;
• Active, known, or suspected autoimmune disease. Type I diabetes mellitus, hypothyroidismonly
requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are allowed

• cN0 anche se stadio IV;
• Evidenza clinica o radiologica dio metastasi a distanza (M1);
• Sede primitive ignota;
• Precedente radioterapia nel distretto cervicocefalico;
• Tumori primitivi sincroni;
• Altra neoplasia solida entro 5 aa dalla diagnosi della presente;
• Malattie autoimmune in atto, attive, sospette. Sono permessi: diabete mellito tipo I, ipotiroidismo che richiedere terapia sostitutiva, disordini cutanei (vitiligo, psoriasi o alopecia) che non richiedono terapia sistemica; condizioni sistemiche che richiedono un evento scatenate noto per verificarsi

E.5 End points

E.5.1

Primary end point(s)

Immunobiomarkers modulation

Variazione negli immunobiomarcatori

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, day 4, 18, 28, before and after postoperative radiotherapy

Basale, giorno 4, giorno 18, giorno 28, primo e ultimo giorno della radioterapia postoperatoria

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

E.6.5

Efficacy

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

Yes

E.8.1.7.1

Other trial design description

Fattibilità

Feasibility

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

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)

According to clinical routine

Secondo pratica clinica

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

2019-09-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-05-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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