Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Mouth Neoplasms

Oral Squamous Cell Carcinoma

Oral Cancer

NBTXR3 activated by IMRT

Christophe LE TOURNEAU, MD-PhD

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.

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.

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.

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

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

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

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

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

Local Progression Free Survival (LPFS) defined as any recurrence at the site of the primary tumor

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

Spots Global Cancer Trial Database for nbtxr3 activated by imrt