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 | No |
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 | |
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 | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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 | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 | 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.8.7 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |