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

A Phase I Dose-Escalation/Dose Expansion Study Of NBTXR3 Activated By Intensity Modulated Radiation Therapy In Patients With Locally Advanced Squamous Cell Carcinoma Of The Oral Cavity Or Oropharynx

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Device: NBTXR3 activated by IMRT

Detailed Description

Patients will receive a single administration of NBTXR3 on day 1,as an intratumor injection, followed by Intensity Modulated Radiation Therapy starting 24 hours later (Day 2), and up to completion of 7 weeks, i.e. 70 Grays, 2Grays/fraction. Patients whose tumor has completely shrunk will be followed for the post-radiotherapy evaluation up to the End of Treatment visit. Those patients whose tumor has not shrunk more than 50% of the baseline size, will stop the radiotherapy and may have a salvage tumor surgery. Then, all patients will be followed every 8 weeks, for the safety evaluation and cancer disease status until the end of the study.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Lille, France, 59000
    • Centre OSCAR LAMBRET
  • Marseille, France, 13385
    • Hôpital La Timone
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75005
    • Institut Curie
  • Rennes, France, 35033
    • CHU Pontchaillou
  • Saint-Priest-en-Jarez, France, 42270
    • Institut de Cancérologie de la Loire Lucien Neuwirth
  • Villejuif, France, 94800
    • Institut Gustave Roussy
• Hungary
  • Budapest, Hungary
    • Hungarian Defense Forces Hospital
  • Budapest, Hungary
    • National Institute of Oncology
• Poland
  • Gliwice, Poland
    • Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach
  • Kielce, Poland
    • Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach
  • Lublin, Poland
    • Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli
  • Tomaszów Mazowiecki, Poland
    • NU-MED, Provita Prolife
  • Zamość, Poland
    • Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością
• Spain
  • Barcelona, Spain
    • Vall d'Hebron Hospital
  • Barcelona, Spain
    • Institut Català d'Oncologia Hospital
  • Madrid, Spain
    • Hospital Universitario Madrid Sanchinarro
  • Madrid, Spain
    • Hospital Fundación Jiménez Díaz
  • Málaga, Spain, 29010
    • Hospital Universitario Regional de Málaga

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• 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

• Adequate function of the liver:

  • AST < or = 5 x ULN
  • ALT < or = 5 x ULN
  • Bilirubin < or = 1.5 x ULN
• Negative pregnancy test ≤ 7 days of NBTXR3 injection in all females of child-bearing potential

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NBTXR3 IntraTumoral injection (IT); Single intratumor injection	Device: NBTXR3 activated by IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Objective Response Rate (ORR) of the primary tumor	The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1	12-24 months
Dose Escalation: Complete Response Rate	The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1	12 months
Dose Expansion: Local Progression Free Survival	Local Progression Free Survival (LPFS) defined as any recurrence at the site of the primary tumor	12-24 months
Dose Expansion: Progression Free Survival	Progression Free Survival (PFS) defined as the time to any progression at the site of the primary tumor, in regional lymph nodes and/or distant metastasis	12-24 months

Collaborators and Investigators

• Sponsor: Nanobiotix
• Investigators: Principal Investigator: Christophe LE TOURNEAU, MD-PhD, Institut Curie Paris France

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2014
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: September 10, 2013
• First Submitted That Met QC Criteria: September 17, 2013
• First Posted (Estimate): September 20, 2013

Study Record Updates

• Last Update Posted (Estimate): December 29, 2022
• Last Update Submitted That Met QC Criteria: December 26, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Oropharynx Cancer; Oral cavity Cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: NBTXR3-102; ID RCB: 2013-A00706-39 (Other Identifier: Other)