NBTXR3 With or Without Cetuximab in LA-HNSCC

Aged Clinical Trial

Official title:

A Phase 3 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 LA-HNSCC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04892173
• Other study ID #: NANORAY-312
• Status: Recruiting
• Phase: Phase 3
• Start date: January 5, 2022
• Est. completion date: January 2026

Study information

• Verified date: December 2022
• Source: Nanobiotix
• Contact: Floris Andriessen
• Phone: +33 (0)7 50 68 90 59
• Email: floris.andriessen[@]nanobiotix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Participants will undergo a screening assessment over a period of ≤28 days to determine eligibility. One primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator

Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following the Investigator's choice, participants will be randomized in a 1:1 ratio on Day:

• Arm A: NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab

• Arm B: Investigator's choice of RT alone or RT in combination with cetuximab

All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period.

An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and will continue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up; withdrawal of consent; or the end of the study, whichever occurs first. Participants who have received further anti-cancer therapy for the study disease and/or have had disease progression/recurrence will be followed only for survival information

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• 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

• Age =65 years

• 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

• For participants with oropharyngeal cancer, human papilloma virus (HPV) p16 status must be known

• 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)

• Has one primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator

• Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one of the following:

1. Aged =75 years

2. Estimated creatinine clearance =30 and <50 mL/min (calculated by Cockcroft and Gault)

3. Hearing loss or tinnitus Grade =2

4. Grade =2 peripheral neuropathy

5. ECOG = 2

6. New York Heart Association (NYHA) class III

• Must be able to tolerate RT with curative intent as determined by the study Investigator.

• 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.

• 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 x upper limit of normal (ULN)

6. Aspartate aminotransferase (AST) =3×ULN

7. Total bilirubin =1.5 mg/dL (in participants 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 participant may be eligible)

8. Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L) if the participant is a candidate for cetuximab treatment as per the Investigator's choice prior to randomization

Exclusion Criteria:

• HNSCC category T1, T2N0, T2N1 or M1 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)

• Has received prior antineoplastic systemic therapy or intervention (including pharmacological - both marketed and investigational, RT, or surgery) for the treatment of HNSCC

• 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 is chosen by the Investigator before randomization)

• 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

• Local regionally recurrent HNSCC that has been previously treated with chemotherapy and/or RT are not eligible for the study

• 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 non-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 New York Heart Association 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 signed ICF through 150 days after the last cetuximab dose/RT fraction. A woman who is =1 year postmenopausal or surgically sterile is not considered to be of childbearing potential.

• Ongoing areca nut (betel nut) consumption within 6 months prior to randomization

• 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

• Subject participating in another clinical study at the time of signature of the informed consent form

Related Conditions & MeSH terms

• Aged
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• NBTXR3
Suspension of inert, crystalline hafnium oxide particles, designed to generate oxygen free radicals to destroy cancer cells after activation by ionizing radiation.
• Cetuximab
Solution for infusion

Radiation:
• Radiation Therapy
Intensity-modulated radiation therapy (IMRT): 70 Gray in 35 fractions over a 7-week period.

Locations

Country	Name	City	State
Austria	Medizinische Universität Graz	Graz
Austria	Ordensklinikum Linz GmbH Barmherzige Schwestern	Linz
Austria	Allgemeines Krankenhaus Wien	Wien
Belgium	Cliniques Universitaires Saint-Luc	Brussel
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven
Bulgaria	Multi-profile Hospital for Active Treatment Uni Hospital	Panagyurishte
Bulgaria	University Specialized Hospital for Active Treatment in Oncology EAD	Sofia
Canada	Jewish General Hospital	Montréal
China	The First Affiliated Hospital of Bengbu Medical College	Fujian
China	The First Affiliated Hospital of Fujian Medical University	Fujian
China	Guangzhou First People's Hospital	Guandong
China	Peking University Shenzhen Hospital	Guandong
China	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangdong
China	Guangxi Medical University Affiliated Wuming Hospital	Guangxi
China	Hubei Cancer Hospital	Hubei
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Hubei
China	Hunan Cancer Hospital	Hunan
China	Affiliated Hospital of Xuzhou Medical University	Jiangxi
China	Jiangxi Cancer Hospital	Jiangxi
China	The Second Affiliated Hospital of Soochow University	Jiangxi
China	Linyi Tumor Hospital	Shandong
China	Qilu Hospital of Shandong University	Shandong
China	Shandong Oncology Hospital	Shandong
China	Shanxi Cancer Hospital	Shanxi
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
Czechia	Olomouc University Hospital	Olomouc
Czechia	Bulovka University Hospital	Prague
Finland	Tampere University Hospital	Tampere
France	Centre Hospitalier Universitaire Amiens-Picardie - Site Sud	Amiens
France	Centre Hospitalier Regional Universitaire Brest	Brest
France	Centre de Lutte contre le Cancer - Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	Hôpital de la Timone	Marseille
France	Ambroise Paré Clinic Group - Hartmann Clinic	Paris
France	Hôpital Européen Georges-Pompidou	Paris
France	Hôpital Tenon	Paris
France	Institut Curie	Paris
France	Hôpital Haut-Lévêque	Pessac
France	Centre de Lutte Contre le Cancer - Centre Henri-Becquerel	Rouen
France	Centre Hospitalier Universitaire de Saint-Étienne	Saint-Étienne
France	Clinique Mutualiste de l'Estuaire	Saint-Nazaire
France	Centre Hospitalier de Valenciennes	Valenciennes
France	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy
France	Institut Gustave Roussy	Villejuif
Georgia	High Technology Hospital MedCenter	Batumi
Georgia	Evex Hospitals - Kutaisi Referral Hospital	Kutaisi
Georgia	LLC Todua Clinic	Tbilisi
Georgia	Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic	Tbilisi
Germany	University Hospital Cologne	Cologne
Germany	Universitätsklinikum Gießen und Marburg	Gießen
Germany	Hanover Medical School	Hanover
Germany	Jena University Hospital	Jena
Germany	Rechts der Isar Hospital of the Technical University of Munich	Munich
Germany	Rostock University Medical Center	Rostock
Germany	Universitätsklinikum Ulm	Ulm
Greece	"Attikon" University General Hospital	Attikí
Greece	University General Hospital of Larissa	Larissa
Greece	Interbalkan Medical Center of Thessaloniki	Thessaloníki
Hungary	Hungarian Defence Forces Medical Centre	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	Albert Szent-Györgyi Health Center	Szeged
Israel	Samson Assuta Ashdod University Hospital	Ashdod
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kindai University Hospital	Osaka
Japan	Osaka Prefectural Hospital Organization - Osaka International Cancer Institute	Osaka
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon
Portugal	Hospital de Braga	Braga
Portugal	Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria	Lisboa
Portugal	Hospital CUF Descobertas	Santarém
Romania	Institutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu	Bucharest
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade
Serbia	Vojnomedicinska Akademija	Belgrade
Serbia	Institute of Oncology of Vojvodina	Sremska Kamenica
Serbia	Clinical Center Kragujevac	Sumadija
Spain	Hospital Universitario Cruces	Barakaldo
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebrón	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Complejo Hospitalario de Navarra	Pamplona
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Taiwan	ChangHua Christian Hospital	Chang Hua
Taiwan	National Cheng Kung University (NCKU) Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of California San Francisco	San Francisco	California
United States	Richmond University Medical Center	Staten Island	New York
United States	Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nanobiotix

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  China,  Czechia,  Finland,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Japan,  Korea, Republic of,  Portugal,  Romania,  Serbia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Time from randomization to local-regional recurrence, local-regional progression, distant progression, or death from any cause, whichever occurs first	30 months following first randomized participant
Secondary	Overall Survival (OS)	Time from randomization to death from any cause	48 months following first randomized participant
Secondary	Local-regional control	Time to local regional progression: time from Randomization to local-regional progression or death, whichever occurs first	48 months following first randomized participant
Secondary	Distant control	Time to distant progression: time from Randomization to distant progression or death, whichever occurs first	48 months following first randomized participant
Secondary	Objective Response Rate (ORR)	Rate of complete response (CR)+partial response (PR) [RESIST 1.1]	48 months following first randomized participant
Secondary	Duration of Overall Response	Time from CR or PR to progression of disease, unequivocal clinical progression, or death, whichever occurs first	48 months following first randomized participant
Secondary	Quality of Life over time - QLQ H&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&N35)	48 months following first randomized participant
Secondary	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	48 months following first randomized participant
Secondary	Safety across duration of study - AEs	Adverse events (AEs)	48 months following first randomized participant