NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx
- Conditions
- Head and Neck Cancer
- Interventions
- Device: NBTXR3 activated by IMRT
- Registration Number
- NCT01946867
- Lead Sponsor
- Nanobiotix
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 75
Not provided
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NBTXR3 IntraTumoral injection (IT) NBTXR3 activated by IMRT Single intratumor injection
- Primary Outcome Measures
Name Time Method Dose Expansion: Overall Response Rate 12-24 months The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Dose Escalation: Determination of the Recommended Phase 2 Dose 12 months The recommended Phase II dose (RD) of NBTXR3 administered as intratumor injection, activated by Intensity Modulated Radiation Therapy (IMRT)
Dose Escalation: Incidence of DLTs and determination of the Recommended Phase 2 Dose 12 months The incidence of early DLTs (early adverse effects related to NBTXR3, as an intratumor injection, activated by IMRT)
Dose Expansion: Complete Response Rate 12-24 months The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
- Secondary Outcome Measures
Name Time Method Dose Escalation: Objective Response Rate (ORR) of the primary tumor 12-24 months The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Dose Escalation: Complete Response Rate 12 months The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Dose Expansion: Local Progression Free Survival 12-24 months Local Progression Free Survival (LPFS) defined as any recurrence at the site of the primary tumor
Dose Expansion: Progression Free Survival 12-24 months 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
Trial Locations
- Locations (20)
Hungarian Defense Forces Hospital
🇭🇺Budapest, Hungary
Hospital Fundación Jimenez Diaz
🇪🇸Madrid, Spain
Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach
🇵🇱Gliwice, Poland
Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
🇵🇱Lublin, Poland
Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością
🇵🇱Zamość, Poland
Centre Francois Baclesse
🇫🇷Caen, France
Hôpital La Timone
🇫🇷Marseille, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Institut de Cancérologie de la Loire Lucien Neuwirth
🇫🇷Saint-Priest-en-Jarez, France
Institut Curie
🇫🇷Paris, France
CHU Pontchaillou
🇫🇷Rennes, France
Institut Gustave Roussy
🇫🇷Villejuif, France
National Institute of Oncology
🇭🇺Budapest, Hungary
NU-MED, Provita Prolife
🇵🇱Tomaszów Mazowiecki, Poland
Institut Catala d'Oncologia Hospital
🇪🇸Barcelona, Spain
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Hospital Universitario Madrid Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario Regional de Malaga
🇪🇸Málaga, Spain
Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach
🇵🇱Kielce, Poland