Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

NBTXR3 With or Without Cetuximab in LA-HNSCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04892173
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : April 4, 2022
Sponsor:
Information provided by (Responsible Party):
Nanobiotix

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:

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.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 5, 2022
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : January 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

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 Name: 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 Name: Erbitux

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




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: 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 :
  1. Overall Survival (OS) [ Time Frame: 48 months following first randomized participant ]
    Time from randomization to death from any cause

  2. Local-regional control [ Time Frame: 48 months following first randomized participant ]
    Time to local regional progression: time from Randomization to local-regional progression or death, whichever occurs first

  3. Distant control [ Time Frame: 48 months following first randomized participant ]
    Time to distant progression: time from Randomization to distant progression or death, whichever occurs first

  4. Objective Response Rate (ORR) [ Time Frame: 48 months following first randomized participant ]
    Rate of complete response (CR)+partial response (PR) [RESIST 1.1]

  5. Duration of Overall Response [ Time Frame: 48 months following first randomized participant ]
    Time from CR or PR to progression of disease, unequivocal clinical progression, or death, whichever occurs first

  6. Quality of Life over time - QLQ H&N35 [ Time Frame: 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)

  7. Quality of Life over time - EQ 5D 5L [ Time Frame: 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

  8. Safety across duration of study - AEs [ Time Frame: 48 months following first randomized participant ]
    Adverse events (AEs)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    1. Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)
    2. Hearing loss or tinnitus Grade ≥2
    3. Grade ≥2 peripheral neuropathy
    4. ECOG >2
    5. 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:

    1. Hemoglobin >9.0 g/dL
    2. Platelet count >100,000 cells/mm3
    3. Leukocytes >3000 cells/mm3
    4. Absolute neutrophil count >1500 cells/mm3
    5. Alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN)
    6. Aspartate aminotransferase (AST) ≤3×ULN
    7. 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)
    8. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04892173


Contacts
Layout table for location contacts
Contact: Marion Kunegel +33 (0)6 84 12 44 49 marion.kunegel@nanobiotix.com
Contact: Peggy Galluzzi +1 (862) 221-6200 peggy.galluzzi@nanobiotix.com

Locations
Show Show 18 study locations
Sponsors and Collaborators
Nanobiotix
Investigators
Layout table for investigator information
Principal Investigator: Christophe Le Tourneau, MD, PhD institute Curie
Principal Investigator: Sue Yom, MD, PhD University of San Francisco
Layout table for additonal information
Responsible Party: Nanobiotix
ClinicalTrials.gov Identifier: NCT04892173    
Other Study ID Numbers: NANORAY-312
First Posted: May 19, 2021    Key Record Dates
Last Update Posted: April 4, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nanobiotix:
LA-HNSCC
NBTXR3
hafnium oxide
radioenhancer
Radiotherapy
RT
HNSCC
Additional relevant MeSH terms:
Layout table for MeSH terms
Squamous Cell Carcinoma of Head and Neck
Carcinoma, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents