NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx

NCT01946867 | Unknown DMC

• 2 other identifiers: NBTXR3-102ID RCB: 2013-A00706-39
• Study Type: interventional
• Target: 75
• Locations: 4 countries
• Sites: 20

Brief Summary

RATIONALE: Cancers of the oral cavity represent 30% of head and neck carcinomas in the western world. The oropharynx is the posterior continuation of the oral cavity and connects with the nasopharynx (above) and laryngopharynx (below). It is also a frequent site of primary head and neck cancers. These structures play a crucial role in swallowing, breath and speech. Locally advanced oropharyngeal cancers can obstruct the air flow or infiltrate muscles or nerves, which significantly disturb local functions. The incidence of Head and Neck Squamous Cell Cancer in patients older 65 years is high, 47% occurred in this population as recorded by the Surveillance, Epidemiology, and End Results registries in the United States. Regarding the therapeutic strategies, the association of radiotherapy with chemotherapy or biologics has demonstrated significant improvement of outcomes with the drawback of higher toxicity, or as demonstrated by 2 meta-analyses, without survival improvement in older patients. NBTXR3 and radiation therapy may increase the cancer cell killing and complete tumor shrinkage allowing a definitive treatment and preservation of local structures and functions in patients older 65 years, who cannot receive cisplatin.

Conditions

Head and Neck Cancer

Keywords

Oral cavity Cancer; Oropharynx Cancer

Outcome Measures

Primary Outcomes (4)

• Dose Escalation: Incidence of DLTs and determination of the Recommended Phase 2 Dose

  The incidence of early DLTs (early adverse effects related to NBTXR3, as an intratumor injection, activated by IMRT)

  12 months

• Dose Escalation: Determination of the Recommended Phase 2 Dose

  The recommended Phase II dose (RD) of NBTXR3 administered as intratumor injection, activated by Intensity Modulated Radiation Therapy (IMRT)

  12 months

• Dose Expansion: Overall Response Rate

  The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1

  12-24 months

• Dose Expansion: Complete Response Rate

  The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1

  12-24 months

Secondary Outcomes (4)

• Dose Escalation: Objective Response Rate (ORR) of the primary tumor

  12-24 months

• Dose Escalation: Complete Response Rate

  12 months

• Dose Expansion: Local Progression Free Survival

  12-24 months

• Dose Expansion: Progression Free Survival

  12-24 months

Study Arms (1)

NBTXR3 IntraTumoral injection (IT)

EXPERIMENTAL

Single intratumor injection

Device: NBTXR3 activated by IMRT

Interventions

NBTXR3 activated by IMRT DEVICE

NBTXR3 IntraTumoral injection (IT)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patients aged ≥ 70 years old, or
• Patients aged ≥ 65 years old and \< 70 years old who are unable to receive cisplatin, or
• Patients who have contraindication to cisplatin or that are intolerant to cisplatin or cetuximab or that cannot receive the combination of chemoradiation, regardless the age
• Histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity or oropharynx
• T3 or T4 primary tumor or Stage III or IVA according to AJCC guidelines (8th Edition, 2018)
• No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
• Clinically eligible for intratumor implantation by injection
• Karnofsky Performance Status ≥ 70
• Adequate function of Bone marrow:
• White Blood Cell (WBC) \> 3.0 x 10\^9/L
• Absolute neutrophil count (ANC) \> or = 1.0 x 10\^9/L
• Platelet count \> or = 100 x 10\^9/L
• Hemoglobin \> or = 9.0 g/dL
• Adequate function of Kidney:
• o Creatinine \< or = 3.0 x ULN or creatinine clearance \> or = 30 mL/min/1.73m²

You may not qualify if:

• Written Informed Consent not obtained, signed and dated
• Prior radiotherapy to any area within the planned radiotherapy field
• Tumor-related dyspnea
• Tumor ulceration which implies vascular risk
• Non measurable disease as defined by RECIST criteria
• History of stroke, CABG, or significant blockage of carotid arteries or coronary arteries or current blockage of coronary or carotid arteries equal to or in excess of 50% blockage
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive heart failure, acute coronary syndrome, etc.
• Medical history of life-threatening ventricular arrhythmia
• Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years
• Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study
• Patients unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures or those with severe psychiatric illness/social situations that would limit compliance with study requirements
• Patients participating in another clinical investigation at the time of signature of the informed consent.

Sponsors & Collaborators

• Nanobiotix: lead

Study Sites (20)

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Hôpital La Timone

Marseille, 13385, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

Institut de Cancérologie de la Loire Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Hungarian Defense Forces Hospital

Budapest, Hungary

Location

National Institute of Oncology

Budapest, Hungary

Location

Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach

Gliwice, Poland

Location

Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach

Kielce, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli

Lublin, Poland

Location

NU-MED, Provita Prolife

Tomaszów Mazowiecki, Poland

Location

Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością

Zamość, Poland

Location

Institut Catala d'Oncologia Hospital

Barcelona, Spain

Location

Vall d'Hebron Hospital

Barcelona, Spain

Location

Hospital Fundación Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, Spain

Location

Hospital Universitario Regional de Malaga

Málaga, 29010, Spain

Location

Related Publications (2)

• Le Tourneau C, Liem X, Nguyen F, Deraedt S, Salas S, Calugaru V, Serrahima MP, Wong Hee Kam S, Hoffmann C, Lesnik M, Blanchard P, Poissonnet G, Bozec A, Saada-Bouzid E, Jegoux F, Castelli J, Devisetty K, Lelonge Y, Jadaud E, Houdas L, Debard A, Vivar OI, Finzi L, Serra A, Linares I, Arranz Obispo C, Thariat J, Rambeau A, Fakhry N, Santini L, Giralt J, Brana Garcia I, Barba MS, Gorphe P, Helfferich F, Herczeg A, Papai Z, Fijuth J, Takacsi-Nagy Z. Intratumoral Radioenhancer Nanoparticle NBTXR3 Followed by Radiotherapy in Head and Neck Cancer: A Phase 1 Dose-Expansion Nonrandomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2026 Jan 29:e254939. doi: 10.1001/jamaoto.2025.4939. Online ahead of print.

  PMID: 41609775 DERIVED

• Hoffmann C, Calugaru V, Borcoman E, Moreno V, Calvo E, Liem X, Salas S, Doger B, Jouffroy T, Mirabel X, Rodriguez J, Chilles A, Bernois K, Dimitriu M, Fakhry N, Hee Kam SW, Le Tourneau C. Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. Eur J Cancer. 2021 Mar;146:135-144. doi: 10.1016/j.ejca.2021.01.007. Epub 2021 Feb 16.

  PMID: 33607477 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Mouth Neoplasms; Oropharyngeal Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Study Officials

• Christophe LE TOURNEAU, MD-PhD

  Institut Curie Paris France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study consists of two parts: Dose Escalation and Dose Expansion. This phase I is an open-label non-randomized, dose-escalation/dose expansion study of safety and tolerability evaluation of NBTXR3, administered as an intratumoral implantation by injection, activated by intensity modulated radiation therapy (IMRT), in patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx.

Study Record Dates

• First Submitted: September 10, 2013
• First Posted: September 20, 2013
• Study Start: January 3, 2014
• Primary Completion: February 1, 2023
• Study Completion: February 1, 2023
• Last Updated: December 29, 2022

Record last verified: 2022-12

Locations

HU (2); FR (8); ES (5); PL (5)