Clinical Trials Register

Summary
EudraCT Number:	2021-002163-22
Sponsor's Protocol Code Number:	NANORAY-312
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-12-02
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

Czechia - SUKL

A.2

EudraCT number

2021-002163-22

A.3

Full title of the trial

A Phase 3 (Pivotal Stage) Study of NBTXR3 Activated by Investigator’s Choice of Radiotherapy Alone or Radiotherapy in Combination with Cetuximab for platinum-based Chemotherapy-ineligible Elderly Patients with Locally Advanced Head & Neck Squamous Cell Carcinoma

Klinické hodnocení fáze 3 (pivotní fáze) přípravku NBTXR3 aktivovaného podle výběru zkoušejícího lékaře samotnou radioterapií nebo radioterapií v kombinaci s cetuximabem u starších pacientů nezpůsobilých k chemoterapii založené na platině s lokálně pokročilým skvamocelulárním karcinomem hlavy a krku

A.3.1

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

NBTXR3 with or without cetuximab in Locally Advanced Head & Neck Squamous Cell Carcinoma (LA-HNSCC)

A.4.1

Sponsor's protocol code number

NANORAY-312

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04892173

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	NANOBIOTIX
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Nanobiotix SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Nanobiotix SA
B.5.2	Functional name of contact point	NANORAY-312 CST
B.5.3	Address:
B.5.3.1	Street Address	60 rue de Wattignies
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75012
B.5.3.4	Country	France
B.5.6	E-mail	nanoray-312@nanobiotix.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Erbitux, 5 mg/mL, 20 mL vials
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Cetuximab
D.3.4	Pharmaceutical form	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	CETUXIMAB
D.3.9.1	CAS number	205923-56-4
D.3.9.4	EV Substance Code	SUB01178MIG
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.3.11 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	No
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)	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	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	Yes
D.2.1.1.1	Trade name	Hensify
D.2.1.1.2	Name of the Marketing Authorisation holder	Nanobiotix SA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Hensify
D.3.2	Product code	NBTXR3
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	Intratumoral use
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	No
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	product is a medical device
D.IMP: 3
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	Lavoisier Glucose 30%
D.2.1.1.2	Name of the Marketing Authorisation holder	CDM Lavoisier
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Glucose 30%
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	Intratumoral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glucose monohydrate
D.3.9.1	CAS number	77938-63-7
D.3.9.3	Other descriptive name	GLUCOSE MONOHYDRATE PH. EUR.
D.3.9.4	EV Substance Code	SUB171773
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/V) percent weight/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	No
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)	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

Locally Advanced Head & Neck Squamous Cell Carcinoma

E.1.1.1

Medical condition in easily understood language

The most common type of head and neck cancer is called squamous cell carcinoma coming from the membrane lining the mouth, and the parts of the digestive and respiratory tubes of the neck.

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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate survival outcomes in subjects treated with intratumorally injected NBTXR3 activated by investigator’s choice of RT alone or RT in combination with cetuximab in comparison to Investigator’s choice alone hereafter referred to as NBTXR3/RT±cetuximab versus RT±cetuximab

E.2.2

Secondary objectives of the trial

To evaluate long-term survival outcomes of NBTXR3/RT±cetuximab versus RT±cetuximab

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

24-hr ECG evaluation sub-study (at selected sites)

E.3

Principal inclusion criteria

_Signed informed consent form (ICF) indicating that the subject understands the purpose of, andprocedures required for the study, and is willing to participate in the study
_Age ≥65 years
_Biopsy-confirmed SCC of the oral cavity, oropharynx, hypopharynx or supraglottic larynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provideconfirmation of SCC
_For subjects with oropharyngeal cancer, HPV status must be known
_Tumor categories T3-T4 according to the 8th edition of the American Joint Committee on CancerStaging Manual (AJCC v8)
_Has at least 1 tumor lesion that can be accurately measured according to RECIST 1.1 (per the central imaging vendor) and is amenable for intratumoral injection, as determined by the Investigator
_A single invaded, biopsy confirmed, accessible LN in the neck of ≥3 cm and <10 cm and with <180-degree encasement of the carotid artery on MRI or CT scan is eligible for intranodal injection
_If a LN is selected for injection, 1 of the 2 injected lesions must be the primary tumor itself
_Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least 1 of the following:
1. Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)
2. Hearing loss or tinnitus Grade ≥2
3. Grade ≥2 peripheral neuropathy
4. ECOG >2
5. Recent cardiac dysfunction (history of unstable angina pectoris, myocardial infarction, or NewYork Heart Association (NYHA) Class III chronic heart failure <3 years prior to screening)
_Must be able to tolerate RT with curative intent as determined by the study Investigator.
_Amenable to definitive treatment with RT. For subjects with an oral cavity cancer the decision for definitive treatment with RT requires consultation with the head and neck surgeon, and the site's multidisciplinary tumor board.
_ECOG performance status of 0 to ≤2
_Life expectancy ≥6 months
_Adequate organ and bone marrow function at screening as defined by:
1. Hemoglobin >9.0 g/dL
2. Platelet count >100,000 cells/mm3
3. Leukocytes >3000 cells/mm3
4. Absolute neutrophil count >1500 cells/mm3
5. Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN)
6. Aspartate aminotransferase (AST) ≤3×ULN
7. Total bilirubin ≤1.5 mg/dL (in subjects with Gilbert's syndrome, if total bilirubin is >1.5×ULN,measure direct and indirect bilirubin and if direct bilirubin is ≤1.5×ULN, the subject may be eligible)
8. Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L)

E.4

Principal exclusion criteria

_HNSCC category T1, T2 or M1 according to the 8th edition of AJCC v8
_Has received prior antineoplastic systemic therapy or intervention (including pharmacological - both marketed and investigational, RT, or surgery) for the treatment of HNSCC
_Subjects with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab must be excluded from cetuximab treatment by the Investigator
_Known history of HIV, active hepatitis B, or active hepatitis C infection
_Local regionally recurrent HNSCC
_Ulceration or other characteristics that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding
_SCC originating in the nasopharynx or paranasal sinus, from the salivary gland, or thyroid gland, or on-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin
_Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
_Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second- or third-degree atrioventricular heart block without a permanent pacemaker in place)
_Class IV congestive heart failure as defined by the NYHA functional classification system <6 months prior to screening
_A pregnant or nursing woman, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from the time that the ICF is signed through 150 days after the last cetuximab dose/RT fraction. A woman who is 2 years postmenopausal or surgically sterile is not considered to be of childbearing potential.
_A known history of areca nut (betel nut) consumption for 10 years or more
_Any condition for that, in the opinion of the Investigator, participation would not be in the best interest of the individual (e.g., compromises the subject's well-being) or that could prevent, limit, or confound the protocol/CIP specified assessments
_Subject participating in another clinical study, except for a non interventional trial/registry at the time of signing the ICF

E.5 End points

E.5.1

Primary end point(s)

PFS: time from randomization to local-regional recurrence, local-regional progression, distant progression, or death from any cause, whichever occurs first

E.5.1.1

Timepoint(s) of evaluation of this end point

ITT population.

E.5.2

Secondary end point(s)

OS: time from randomization to death from any cause

E.5.2.1

Timepoint(s) of evaluation of this end point

ITT population.

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

Yes

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)

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

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

Yes

E.8.2.3.1

Comparator description

NBTXR3 (medical device) in addition to investigator's choice of RT (+/-cetuximab)

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

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Georgia

Philippines

Serbia

Austria

Belgium

Bulgaria

Canada

China

Croatia

Czechia

Finland

Hungary

India

Israel

Japan

Malaysia

Portugal

Romania

Russian Federation

Spain

Sweden

Switzerland

Ukraine

United Kingdom

United States

France

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

the date when the required number of PFS (progression-free survival) and OS (overall survival) events have occurred.

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

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)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

500

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

367

F.4.2.2

In the whole clinical trial

500

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)

Post-RT neck dissection

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	TTCC
G.4.3.4	Network Country	Spain
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	GORTEC
G.4.3.4	Network Country	France
G.4 Investigator Network to be involved in the Trial: 3
G.4.1	Name of Organisation	GONO
G.4.3.4	Network Country	Italy

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-12-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-01-10

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

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