NBTXR3 With or Without Cetuximab in LA-HNSCC

JRCT ID: jRCT2051220124

Registered date:01/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Locally Advanced Head and Neck Squamous Cell Carcinoma
• Date of first enrollment: 22/09/2023
• Target sample size: 20
• Countries of recruitment: Austria,Japan,Belgium,Japan,Bulgaria,Japan,Canada,Japan,China,Japan,Croatia,Japan,Czech Republic,Japan,Finland,Japan,France,Japan,Georgia,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Israel,Japan,Portugal,Japan,Romania,Japan,Serbia,Japan,South Korea,Japan,Spain,Japan,Sweden,Japan,Switzerland,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan,Brazil,Japan,India,Japan,Italy,Japan,Philippines,Japan
• Study type: Interventional

Intervention(s)

Experimental: Arm A
NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT incombination with cetuximab. NBTXR3 is given as a single intratumoral injection as a dose of 33% of the Gross Tumor Volume
Drug: NBTXR3
Radiation: Radiation Therapy (in combination with cetuximab by investigator's choice)

Active Comparator: Arm B
Investigator's choice of RT alone or RT in combination with cetuximab
Radiation: Radiation Therapy (in combination with cetuximab by investigator's choice)

Outcome(s)

• Primary Outcome: Progression-free Survival (PFS)
• Secondary Outcome: Overall Survival (OS)

Key inclusion & exclusion criteria

• Age minimum: >= 60age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Signed informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for the study, and is willing to participate in the study.
2. Age >=60 years.
3. Biopsy-confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provide confirmation of SCC.
4. For participants with oropharyngeal cancer, human papilloma virus (HPV) status must be known.
5. Tumor categories T3-T4 any N or T2 if >=N2 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8).
6. Has one primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator.
7. Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one 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 performance status=2
e. New York Heart Association (NYHA) class III
OR
Aged 70-74 with Geriatric 8 (G8) score <=14 or aged >=75 years
8. Must be able to tolerate RT with curative intent as determined by the study Investigator.
9. Amenable to definitive treatment with RT. Participants with an oral cavity cancer should not be eligible to the primary standard treatment, which is surgery, and the decision for definitive treatment with RT requires consultation with the head and neck surgeon and the site's multidisciplinary tumor board.
10. ECOG performance status of 0 to <=2.
11. Life expectancy >=6 months.
12. Adequate organ and bone marrow function at screening as defined by:
a. Hemoglobin >9.0 g/dL
b. Platelet count >=100,000 cells/mm^3
c. Leukocytes >3000 cells/mm^3
d. Absolute neutrophil count >1500 cells/mm^3
e. Alanine aminotransferase <=3 x upper limit of normal (ULN)
f. Aspartate aminotransferase <=3xULN
g. Total bilirubin <=1.5 mg/dL (in participants with Gilbert's syndrome, if total bilirubin is >1.5xULN, measure direct and indirect bilirubin and if direct bilirubin is <=1.5xULN, the participant may be eligible)
h. Total serum magnesium within normal ranges if the participant is a candidate for cetuximab treatment as per the Investigator's choice prior to randomization
i. Estimated creatinine clearance >=30 mL/min (calculated by Cockcroft and Gault)

Exclude criteria

1. HNSCC category T1, T2 N0, T2 N1, or M1 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (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. Participants with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab and participants with known prior or ongoing interstitial lung disease must be excluded as a candidate for cetuximab treatment as per the Investigator's choice before randomization (these participants can still be eligible for the study, only if RT alone or NBTXR3+RT alone is chosen and documented by the Investigator before randomization).
4. Known history of human immunodeficiency virus (HIV)
Chronically ongoing active hepatitis B, or chronically ongoing active hepatitis C infection as defined in AASLD (American Association for the Study of Liver Diseases)/EASL (European Association for the Study of the Liver) guidelines.
5. Loco-regionally recurrent HNSCC that has been previously treated with surgery, chemotherapy, and/or RT are not eligible for the study.
6. Ulceration or other characteristics (e.g., bleeding diathesis) that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding.
7. SCC originating in the nasopharynx, 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 (including a second synchronous HNSCC) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, except when:
The risk of the prior malignancy interfering with either safety or efficacy endpoints is very low; and if all treatment of that malignancy was completed at least 2 years before randomization and the participant has no clinical evidence of disease recurrence.
This exception includes completely resected/treated non-melanoma skin cancer, cervical uterine cancer, T1 N0 M0 invasive hormone-sensitive breast cancer, hormone-sensitive prostate cancer with a Gleason score of <=6, and completely resected non-muscle invasive bladder cancer.
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 New York Heart Association 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 signed ICF through 150 days after the last cetuximab dose/RT fraction. A woman who is >=1 year postmenopausal or who is surgically sterile is not considered to be of child bearing potential (pregnancy test is not required). Nursing woman could not be included in the study even in the case of breastfeeding suspension as the breastfeeding resumption could not occur during the study.
12. 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 participant's well-being) or that could prevent, limit, or confound the protocol/CIP specified assessments, including subjects under legal protection.
13. Subject participating in another clinical study at the time of signature of the informed consent form.

Related Information

• Primary Sponsor: Floris Andriessen
• Secondary ID(s): NCT04892173,2021-002163-22