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NBTXR3 With or Without Cetuximab in LA-HNSCC

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ClinicalTrials.gov Identifier: NCT04892173
Recruitment Status : Recruiting
First Posted : May 19, 2021
Last Update Posted : January 3, 2023
Sponsor:
Information provided by (Responsible Party):
Nanobiotix

Study Description
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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 Aged 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. One primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator

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. Participants who have received further anti-cancer therapy for the study disease and/or have had disease progression/recurrence will be followed only for survival information

Study Design
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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

Arms and Interventions
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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.


Outcome Measures
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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)


Eligibility Criteria
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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 any N or T2, if ≥N2 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8)
  • Has one primary tumor lesion that is amenable for intratumoral injection, as determined by the Investigator

  • Ineligible to receive platinum-based chemotherapy for the treatment of LA HNSCC as defined by having at least one of the following:

    1. Aged ≥75 years
    2. Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault)
    3. Hearing loss or tinnitus Grade ≥2
    4. Grade ≥2 peripheral neuropathy
    5. ECOG = 2
    6. New York Heart Association (NYHA) class III
  • Must be able to tolerate RT with curative intent as determined by the study Investigator.
  • Amenable to definitive treatment with RT. Participants with an oral cavity cancer, should not be eligible to the primary standard treatment, which is surgery, and 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 x 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) if the participant is a candidate for cetuximab treatment as per the Investigator's choice prior to randomization

Exclusion Criteria:

  • HNSCC category T1, T2N0, T2N1 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 and participants with known prior or ongoing interstitial lung disease must be excluded as a candidate for cetuximab treatment as per the Investigator's choice before randomization (these participants can still be eligible for the study, only if RT alone is chosen by the Investigator before randomization)
  • Known history of human immunodeficiency virus (HIV) Chronically ongoing active hepatitis B, or chronically ongoing active hepatitis C infection as defined in AASLD (American Association for the Study of Liver Diseases)/EASL (European Association for the Study of the Liver) guidelines
  • Local regionally recurrent HNSCC that has been previously treated with chemotherapy and/or RT are not eligible for the study
  • 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 ≥1 year postmenopausal or surgically sterile is not considered to be of childbearing potential.
  • Ongoing areca nut (betel nut) consumption within 6 months prior to randomization
  • 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, including subjects under legal protection
  • Subject participating in another clinical study at the time of signature of the informed consent form
Contacts and Locations
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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
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Contact: Floris Andriessen +33 (0)7 50 68 90 59 floris.andriessen@nanobiotix.com
Contact: Peggy Galluzzi +1 (862) 221-6200 peggy.galluzzi@nanobiotix.com

Locations
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Sponsors and Collaborators
Nanobiotix
Investigators
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Principal Investigator: Christophe Le Tourneau, MD, PhD Institute Curie
Principal Investigator: Sue Yom, MD, PhD University of San Francisco
Principal Investigator: Jinming Yu, MD, PhD Shandong Cancer Hospital and Institute
More Information
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Responsible Party: Nanobiotix
ClinicalTrials.gov Identifier: NCT04892173    
Other Study ID Numbers: NANORAY-312
First Posted: May 19, 2021    Key Record Dates
Last Update Posted: January 3, 2023
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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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