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

Nanobiotix

Status

Active, not recruiting

Conditions

Head and Neck Cancer

Treatments

Device: NBTXR3 activated by IMRT

Study type

Interventional

Funder types

Industry

Identifiers

NCT01946867

NBTXR3-102

ID RCB: 2013-A00706-39 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

75 patients

Sex

All

Ages

65+ years old

Volunteers

No Healthy Volunteers

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.