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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Nanobiotix
- Enrollment
- 75
- Locations
- 29
- Primary Endpoint
- Dose Expansion: Overall Response Rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
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.
Outcomes
Primary Outcomes
Dose Expansion: Overall Response Rate
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 12-24 months
The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Secondary Outcomes
- Dose Escalation: Objective Response Rate (ORR) of the primary tumor(12-24 months)
- Dose Expansion: Local Progression Free Survival(12-24 months)
- Dose Expansion: Progression Free Survival(12-24 months)
- Dose Escalation: Complete Response Rate(12 months)