Clinical trial NCT01946867: NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Head and Neck Cancer
Keywords: Oral cavity Cancer
Oropharynx Cancer
Lead sponsor: Nanobiotix
Sponsor class: INDUSTRY
First posted: 2013-09-20
Enrollment: 75
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation: Incidence of DLTs and determination of the Recommended Phase 2 Dose
timeFrame: 12 months
measure: Dose Escalation: Determination of the Recommended Phase 2 Dose
timeFrame: 12 months
measure: Dose Expansion: Overall Response Rate
timeFrame: 12-24 months
measure: Dose Expansion: Complete Response Rate
timeFrame: 12-24 months
Secondary outcomes:
measure: Dose Escalation: Objective Response Rate (ORR) of the primary tumor
timeFrame: 12-24 months
measure: Dose Escalation: Complete Response Rate
timeFrame: 12 months
measure: Dose Expansion: Local Progression Free Survival
timeFrame: 12-24 months
measure: Dose Expansion: Progression Free Survival
timeFrame: 12-24 months
Other outcomes:
Locations:
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Hôpital La Timone
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Rennes
country: France
facility: CHU Pontchaillou
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire Lucien Neuwirth
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Budapest
country: Hungary
facility: Hungarian Defense Forces Hospital
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Gliwice
country: Poland
facility: Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach
city: Kielce
country: Poland
facility: Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
city: Tomaszów Mazowiecki
country: Poland
facility: NU-MED, Provita Prolife
city: Zamość
country: Poland
facility: Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia Hospital
city: Barcelona
country: Spain
facility: Vall d'Hebron Hospital
city: Madrid
country: Spain
facility: Hospital Fundación Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Malaga
Study officials:
affiliation: Institut Curie Paris France
name: Christophe LE TOURNEAU, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.