NBTXR3 With or Without Cetuximab in LA-HNSCC

Sponsor

Nanobiotix (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04892173

Collaborator

(none)

500

Enrollment

Locations

Arms

47.9

Anticipated Duration (Months)

27.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a global, open-label, randomized, 2-arm, Investigator's choice Phase 3 (Pivotal Stage) study to investigate the efficacy/performance and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with LA-HNSCC.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Head and Neck Squamous Cell Carcinoma	Drug: NBTXR3 Drug: Cetuximab Radiation: Radiation Therapy	Phase 3

Detailed Description

Participants will undergo a screening assessment over a period of ≤28 days to determine eligibility. At least 1 or 2 measurable target lesion(s) per RECIST 1.1 that is/are amenable for intratumoral/intranodal injection must be present as determined by the Investigator.

Participants must have a single invaded lymph node to be eligible for intranodal injection.

Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following the Investigator's choice, participants will be randomized in a 1:1 ratio on Day:

Arm A: NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab
Arm B: Investigator's choice of RT alone or RT in combination with cetuximab

All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period.

An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and will continue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up; withdrawal of consent; or the end of the study, whichever occurs first. Patients who have received further anti-cancer therapy and/or have had disease progression/recurrence will be followed only for survival information

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3 Study of NBTXR3 Activated by Investigator's Choice of Radiotherapy Alone or Radiotherapy in Combination With Cetuximab for Platinum-based Chemotherapy-Ineligible Elderly Patients With LA-HNSCC

Actual Study Start Date :

Jan 5, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jan 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. NBTXR3 is given as a single intratumoral injection as a dose of 33% of the Gross Tumor Volume	Drug: NBTXR3 Suspension of inert, crystalline hafnium oxide particles, designed to generate oxygen free radicals to destroy cancer cells after activation by ionizing radiation. Other Names: Functionalized hafnium oxide nanoparticles Radiation: Radiation Therapy Intensity-modulated radiation therapy (IMRT): 70 Gray in 35 fractions over a 7-week period.
Active Comparator: Arm B Investigator's choice of RT alone or RT in combination with cetuximab	Drug: Cetuximab Solution for infusion Other Names: Erbitux Radiation: Radiation Therapy Intensity-modulated radiation therapy (IMRT): 70 Gray in 35 fractions over a 7-week period.

Arm

Intervention/Treatment

Experimental: Arm A

NBTXR3, as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. NBTXR3 is given as a single intratumoral injection as a dose of 33% of the Gross Tumor Volume

Drug: NBTXR3

Suspension of inert, crystalline hafnium oxide particles, designed to generate oxygen free radicals to destroy cancer cells after activation by ionizing radiation.

Other Names:

Functionalized hafnium oxide nanoparticles

Radiation: Radiation Therapy

Intensity-modulated radiation therapy (IMRT): 70 Gray in 35 fractions over a 7-week period.

Active Comparator: Arm B

Investigator's choice of RT alone or RT in combination with cetuximab

Drug: Cetuximab

Solution for infusion

Other Names:

Erbitux

Radiation: Radiation Therapy

Intensity-modulated radiation therapy (IMRT): 70 Gray in 35 fractions over a 7-week period.

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) [30 months following first randomized participant]
Time from randomization to local-regional recurrence, local-regional progression, distant progression, or death from any cause, whichever occurs first

Secondary Outcome Measures

Overall Survival (OS) [48 months following first randomized participant]
Time from randomization to death from any cause
Local-regional control [48 months following first randomized participant]
Time to local regional progression: time from Randomization to local-regional progression or death, whichever occurs first
Distant control [48 months following first randomized participant]
Time to distant progression: time from Randomization to distant progression or death, whichever occurs first
Objective Response Rate (ORR) [48 months following first randomized participant]
Rate of complete response (CR)+partial response (PR) [RESIST 1.1]
Duration of Overall Response [48 months following first randomized participant]
Time from CR or PR to progression of disease, unequivocal clinical progression, or death, whichever occurs first
Quality of Life over time - QLQ H&N35 [48 months following first randomized participant]
Change from baseline over time in symptoms, function, and health related QOL using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire-Head and Neck Cancer Module (QLQ H&N35)
Quality of Life over time - EQ 5D 5L [48 months following first randomized participant]
Change from baseline over time in symptoms, function, and health related QOL using the 5 level EuroQol 5 dimension (EQ 5D 5L) instrument
Safety across duration of study - AEs [48 months following first randomized participant]
Adverse events (AEs)

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for the study, and is willing to participate in the study
Age ≥65 years
Biopsy-confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provide confirmation of SCC
For participants with oropharyngeal cancer, human papilloma virus (HPV) p16 status must be known
Tumor categories T3-T4 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)
Has at least 1 tumor lesion that can be accurately measured according to RECIST 1.1 (per the Central Imaging vendor) and is amenable for intratumoral injection, as determined by the Investigator
A single invaded, biopsy confirmed, accessible LN in the neck of ≥3 cm and <10 cm and with <180-degree encasement of the carotid artery on MRI or CT scan is eligible for intranodal injection
If a LN is selected for injection, 1 of the 2 injected lesions must be the primary tumor itself
Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one of the following:

Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)
Hearing loss or tinnitus Grade ≥2
Grade ≥2 peripheral neuropathy
ECOG >2
Recent cardiac dysfunction (history of unstable angina pectoris, myocardial infarction, or New York Heart Association (NYHA) class III chronic heart failure <3 years prior to screening)

Must be able to tolerate RT with curative intent as determined by the study Investigator.
Amenable to definitive treatment with RT. For subjects with an oral cavity cancer, the decision for definitive treatment with RT requires consultation with the head and neck surgeon and the site's multidisciplinary tumor board.
ECOG performance status of 0 to 2
Life expectancy ≥6 months
Adequate organ and bone marrow function at screening as defined by:

Hemoglobin >9.0 g/dL
Platelet count >100,000 cells/mm3
Leukocytes >3000 cells/mm3
Absolute neutrophil count >1500 cells/mm3
Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN)
Aspartate aminotransferase (AST) ≤3×ULN
Total bilirubin ≤1.5 mg/dL (in participants with Gilbert's syndrome, if total bilirubin is >1.5×ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5×ULN, the participant may be eligible)
Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L)

Exclusion Criteria:

HNSCC category T1, T2 or M1 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)
Has received prior antineoplastic systemic therapy or intervention (including pharmacological - both marketed and investigational, RT, or surgery) for the treatment of HNSCC
Participants with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab must be excluded from cetuximab treatment by the Investigator
Known history of human immunodeficiency virus (HIV), active hepatitis B, or active hepatitis C infection
Local regionally recurrent HNSCC
Ulceration or other characteristics that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding
SCC originating in the nasopharynx or paranasal sinus, from the salivary gland, or thyroid gland, or non-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin
Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second- or third-degree atrioventricular heart block without a permanent pacemaker in place)
Class IV congestive heart failure as defined by the New York Heart Association functional classification system <6 months prior to screening
A pregnant or nursing woman, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from signed ICF through 150 days after the last cetuximab dose/RT fraction. A woman who is 2 years postmenopausal or surgically sterile is not considered to be of childbearing potential.
A known history of areca nut (betel nut) consumption
Any condition for that, in the opinion of the Investigator, participation would not be in the best interest of the individual (e.g., compromises the participant's well-being) or that could prevent, limit, or confound the protocol/CIP specified assessments
Subject participating in another clinical study at the time of signature of the informed consent form

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	12902
2	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven		Belgium
3	Multi-profile Hospital for Active Treatment Uni Hospital	Panagyurishte		Bulgaria
4	University Specialized Hospital for Active Treatment in Oncology EAD	Sofia		Bulgaria
5	Centre de Lutte contre le Cancer - Centre Oscar Lambret	Lille		France
6	Centre Léon Bérard	Lyon		France
7	Hôpital de la Timone	Marseille		France
8	Hôpital Tenon	Paris		France
9	Institut Curie	Paris		France
10	Centre Hospitalier de Valenciennes	Valenciennes		France
11	Institut de Cancérologie de Lorraine	Vandœuvre-lès-Nancy		France
12	Institut Gustave Roussy	Villejuif		France
13	High Technology Hospital MedCenter	Batumi		Georgia
14	LLC Todua Clinic	Tbilisi		Georgia
15	Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic	Tbilisi		Georgia
16	Hospital Universitario Cruces	Barakaldo		Spain
17	Complejo Hospitalario de Navarra	Pamplona		Spain
18	Hospital Universitario Marqués de Valdecilla	Santander		Spain