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CTRI Number  CTRI/2022/12/048448 [Registered on: 23/12/2022] Trial Registered Prospectively
Last Modified On: 22/04/2026
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Multiple Arm Trial 
Public Title of Study   NBTXR3 With or Without Cetuximab in Locally Advanced Head & Neck Squamous Cell Carcinoma (LA-HNSCC) 
Scientific Title of Study   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 
Trial Acronym   
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
2021-002163-22  EudraCT 
NANORAY-312 Amendment 6 dated 15 January 2025  Protocol Number 
NCT04892173  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query
Modification(s)  
Name  Dr Sanish Davis 
Designation  R and D Director GCO India 
Affiliation  Janssen Pharmaceutical Companies of Johnson and Johnson Pvt Ltd. 
Address  Johnson and Johnson Private Limited, Arena Space Jogeshwari East. Mumbai MAHARASHTRA
-
Mumbai
MAHARASHTRA
400060
India 
Phone  919820958943  
Fax    
Email  sdavis20@its.jnj.com  
 
Details of Contact Person
Public Query
Modification(s)  
Name  Dr Sanish Davis 
Designation  R and D Director GCO India 
Affiliation  Janssen Pharmaceutical Companies of Johnson and Johnson Pvt Ltd. 
Address  Johnson and Johnson Private Limited, Arena Space Jogeshwari East. Mumbai MAHARASHTRA
-
Mumbai
MAHARASHTRA
400060
India 
Phone  919820958943  
Fax    
Email  sdavis20@its.jnj.com  
 
Source of Monetary or Material Support
Modification(s)  
Johnson and Johnson Private Limited Arena Space Jogeshwari East Mumbai MAHARASHTRA 
 
Primary Sponsor
Modification(s)  
Name  Johnson and Johnson Private Limited 
Address  L. B. S. Marg, Mulund West Maharashtra, India 400080 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Pharmaceutical Research Associates India Private Limited  Level 2, B- wing, Times Square, Andheri - Kurla Road, Andheri (East), Mumbai – 400059 Maharashtra, India 
 
Countries of Recruitment     Austria
Belgium
Bulgaria
Canada
China
Croatia
Czech Republic
Finland
France
Georgia
Germany
Greece
Hungary
India
Israel
Italy
Japan
Philippines
Portugal
Republic of Korea
Romania
Serbia
Spain
Sweden
Switzerland
Taiwan
United Kingdom
United States of America
Brazil
Ireland  
Sites of Study
Modification(s)  
No of Sites = 5  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Gopichand Mamillapalli  HCG cancer center  Oncology Department 2nd Floor B block 33 25 33 Ch Venkata Krishnayya Street AP 520002
Krishna
ANDHRA PRADESH 		 98 852 56059

mgopichand@yahoo.com 
Dr Rajnish Vasant Nagarkar  HCG Manavata Cancer Centre  Behind Shivang Auto, Mumbai Naka, Nashik – 422002
Nashik
MAHARASHTRA 		 02536661111
02536661129
drraj@manavatacancercentre.com 
Dr Lithika Lavanya M  M S Ramaiah Medical College and Hospitals  Department of Radiation Oncology, M S Ramaiah Nagar, MSRIT Post, Bangalore – 560054
Bangalore
KARNATAKA 		 91 7204569373
91 7204569373
lithikalavanya.rmc@msruas.ac.in 
Dr Munish Gairola  Rajiv Gandhi Cancer Institute and Research Centre  Dept of Radiation Oncology Sector 5 Rohini Delhi
New Delhi
DELHI 		 9958431598

gairola.munish@rgcirc.org 
Dr Vijay Maruti Patil  Tata Memorial Hospital  Department of Medical Oncology, Dr E Borges Road, Parel, Mumbai – 400012
Mumbai
MAHARASHTRA 		 02224177032
02224146392
vijaypgi@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 5  
Name of Committee  Approval Status 
Ethics Committee, MS Ramaiah Medical College and Hospitals  Approved 
IEC HCG Curie City Cancer Centre  Approved 
Institutional Ethics Committee, Tata Memorial Hospital  Approved 
Institutional Review Board RGCI  Approved 
Manavata Clinical Research Institute Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C760||Malignant neoplasm of head, face and neck,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  NBTXR3/Radiotherapy (RT)± cetuximab  Suspension of inert, crystalline hafnium oxide particles, designed to generate oxygen free radicals to destroy cancer cells after activation by ionizing radiation. NBTXR3 injection volume is calculated as a percentage of the computed Gross Tumor Volume (GTV) contour of the lesion(s) by MRI, as determined by the Investigator. The product dose is 33% of the GTV of the lesion(s). Cetuximab: A loading dose of 400 mg/m2 (over 120 minutes) of body-surface area at 1 week prior to the start of RT, followed by weekly infusions of 250 mg/m2 (over 60 minutes) for the duration of RT i.e., upto 64 days. 
Comparator Agent  RadioTherapy ± cetuximab  Cetuximab: A loading dose of 400 mg/m2 (over 120 minutes) of body-surface area at 1 week prior to the start of RT, followed by weekly infusions of 250 mg/m2 (over 60 minutes) for the duration of RT. 
 
Inclusion Criteria
Modification(s)  
Age From  65.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1) Signed informed consent form (ICF) indicating that the subject understands the purpose of, and procedures required for the study, and is willing to participate in the study.
2) 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 provide confirmation of SCC
3) For subjects with oropharyngeal cancer, HPV status must be known
4) Tumor categories T3-T4 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)
5) 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.
6) Ineligible to receive platinum-based chemotherapy for the treatment of LA-HNSCC as defined by having at least 1 of the following:
a) Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)
b) Hearing loss or tinnitus Grade ≥2
c) Grade ≥2 peripheral neuropathy
d) ECOG >2
e) Recent cardiac dysfunction (history of unstable angina pectoris, myocardial infarction, or New York Heart Association (NYHA) Class III chronic heart failure <3 years prior to screening)
7) Must be able to tolerate RT with curative intent as determined by the study Investigator
8) 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
9) ECOG performance status of 0 to ≤2
10) Life expectancy ≥6 months
11) Adequate organ and bone marrow function at screening as defined by:
a) Hemoglobin >9.0 g/dL
b) Platelet count >100,000 cells/mm3
c) Leukocytes >3000 cells/mm3
d) Absolute neutrophil count >1500 cells/mm3
e) ALT ≤3 x upper limit of normal (ULN)
f) AST ≤3 x ULN
g) 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)
h) Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L)
Screening laboratory assessments will be performed by a central laboratory. 
 
ExclusionCriteria 
Details  1) HNSCC category T1, T2, or M1 according to AJCC v8
2) Has received prior antineoplastic systemic therapy or intervention (including pharmacological – both marketed and investigational, RT, or surgery) for the treatment of HNSCC
3) Subjects with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab must be excluded from cetuximab treatment by the Investigator
4) Known history of HIV, active hepatitis B, or active hepatitis C infection
5) Local regionally recurrent HNSCC
6) Ulceration or other characteristics that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding
7) SCC originating in the nasopharynx or paranasal sinus, salivary gland, or thyroid gland, or non-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin
8) Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
9) 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)
10) Class IV congestive heart failure as defined by the NYHA functional classification system <6 months prior to screening
11) 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
12) A known history of areca nut (betel nut) consumption for 10 years or more
13) Any condition 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
14) Subject participating in another clinical study, except for a non-interventional trial/registry, at the time of signing the ICF 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Progression-free Survival (PFS)  time from randomization to
local-regional recurrence, local-regional
progression, distant progression, or death
from any cause, whichever occurs first 
 
Secondary Outcome  
Outcome  TimePoints 
Overall Survival (OS)  time from randomization to death from any cause 
local-regional control of NBTXR3 / RT ± cetuximab versus RT ± cetuximab  Time from randomization to local-regional progression or death, whichever occurs first 
Distant control of NBTXR3 / RT ± cetuximab versus RT ± cetuximab  Time from randomization to distant progression or death whichever occurs first 
tumor response to NBTXR3 / RT ± cetuximab versus RT ± cetuximab  1) Objective Response Rate (as defined by the RECIST 1.1) rate of CR and partial response
2) Duration of Response (as defined by RECIST 1.1) time from CR or PR to progression of disease, unequivocal clinical progression, or death, whichever occurs first 
Cancer-specific event-free survival  time from randomization to local-regional recurrence, local-regional progression, distant progression, or cancer-related death, whichever occurs first 
Cancer-specific survival  time from randomization to cancer-related death 
Quality of Life over time - QLQ H and N35  Change from baseline over time in symptoms, function, and health related QOL using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire Head and Neck Cancer Module (QLQ H and N35) 
Quality of Life over time - EQ 5D 5L  Change from baseline over time in symptoms, function, and health related QOL using the 5 level EuroQol 5 dimension (EQ 5D 5L) instrument 
 
Target Sample Size
Modification(s)  		 Total Sample Size="500"
Sample Size from India="30" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   02/01/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  10/12/2021 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="1"
Days="27" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   None 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary
Modification(s)  		 This is a global, open-label, randomized, 2-arm, Investigator’s choice Phase 3 (Pivotal Stage) study to investigate the efficacy/performance and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with LA-HNSCC. 
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