Summary
EudraCT Number:2021-002163-22
Sponsor's Protocol Code Number:NANORAY-312
National Competent Authority:Germany - PEI
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2021-11-16
Trial results
A. Protocol Information
A.1Member State ConcernedGermany - PEI
A.2EudraCT number2021-002163-22
A.3Full 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
A.3.1Title 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.4.1Sponsor's protocol code numberNANORAY-312
A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04892173
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorNanobiotix SA
B.1.3.4CountryFrance
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportNanobiotix SA
B.4.2CountryFrance
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationNanobiotix SA
B.5.2Functional name of contact pointNANORAY-312 CST
B.5.3 Address:
B.5.3.1Street Address60 rue de Wattignies
B.5.3.2Town/ cityParis
B.5.3.3Post code75012
B.5.3.4CountryFrance
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Erbitux, 5 mg/mL, 20 mL vials
D.2.1.1.2Name of the Marketing Authorisation holderMerck Europe B.V.
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCetuximab
D.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNCETUXIMAB
D.3.9.1CAS number 205923-56-4
D.3.9.4EV Substance CodeSUB01178MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number5
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another 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.1.1Medical condition(s) being investigated
Locally Advanced Head & Neck Squamous Cell Carcinoma
E.1.1.1Medical 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.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.1
E.1.2Level PT
E.1.2Classification code 10067821
E.1.2Term Head and neck cancer
E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main 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.2.2Secondary objectives of the trial
To evaluate long-term survival outcomes of NBTXR3/RT±cetuximab versus RT±cetuximab
E.2.3Trial contains a sub-study Yes
E.2.3.1Full title, date and version of each sub-study and their related objectives
24-hr ECG evaluation sub-study (at selected sites)
E.3Principal 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.4Principal 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.5.1Primary 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.5.1.1Timepoint(s) of evaluation of this end point
ITT population.
E.5.2Secondary end point(s)
OS: time from randomization to death from any cause
E.5.2.1Timepoint(s) of evaluation of this end point
ITT population.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) No
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
NBTXR3 (medical device) in addition to investigator's choice of RT (+/-cetuximab)
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned7
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA18
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Austria
Belgium
Bulgaria
Canada
China
Croatia
Czechia
Finland
France
Georgia
Germany
Greece
Hungary
India
Israel
Italy
Japan
Korea, Republic of
Malaysia
Philippines
Portugal
Romania
Russian Federation
Serbia
Spain
Sweden
Switzerland
Taiwan
Ukraine
United Kingdom
United States
E.8.7Trial 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.8.9.1In the Member State concerned years3
E.8.9.1In the Member State concerned months5
E.8.9.1In the Member State concerned days23
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) No
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 500
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state27
F.4.2 For a multinational trial
F.4.2.1In the EEA 367
F.4.2.2In 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.4.1Name of Organisation TTCC
G.4.3.4Network Country Spain
G.4 Investigator Network to be involved in the Trial: 2
G.4.1Name of Organisation GORTEC
G.4.3.4Network Country France
G.4 Investigator Network to be involved in the Trial: 3
G.4.1Name of Organisation GONO
G.4.3.4Network Country Italy
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-07-13
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-01-25
P. End of Trial
P.End of Trial StatusOngoing