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JNJ-90301900 (NBTXR3) Activated by Radiotherapy With or Without Cetuximab in LA-HNSCC

Phase 3
Recruiting
Conditions
Locally Advanced Head and Neck Squamous Cell Carcinoma
Aged
Interventions
Drug: JNJ-90301900 (NBTXR3)
Radiation: Radiation Therapy
Registration Number
NCT04892173
Lead Sponsor
Johnson & Johnson Enterprise Innovation Inc.
Brief Summary

This is a global, open-label, randomized, 2-arm, Investigator's choice Phase 3 (Pivotal Stage) study to investigate the efficacy and safety of JNJ-90301900 (NBTXR3) / radiation therapy (RT)±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).

Detailed Description

Participants will undergo a screening assessment over a period of less than or equal to (\<=) 28 days to determine eligibility.

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:

* Arm A: JNJ-90301900 (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

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
500
Inclusion Criteria
  • Age greater than or equal to (>=) 60 years old

  • Squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx and a candidate for definitive radiation therapy with or without cetuximab

  • Clinical stage T3-4 NX or T2 N2-3 disease according to the 8th edition of AJCC

  • One primary tumor lesion amendable for intratumoral injection

  • Ineligible to receive platinum-based chemotherapy with radiation (at least one of the following):

    1. Estimated creatinine clearance >= 30 and less than (<) 50 milliliters/minute (mL/min) (per Cockcroft-Gault equation), Grade >= 2 hearing loss or tinnitus, Grade >= 2 peripheral neuropathy, Eastern Cooperative Oncology Group (ECOG) Performance Status 2 or New York Heart Association Class 3
    2. Age 70-74 years old with Geriatric 8 (G8) score less than or equal to (<=) 14
    3. Age >= 75 years old
Exclusion Criteria
  • Carcinoma of the nasopharynx, paranasal sinus(es), salivary gland, thyroid gland, or unknown primary
  • Non-squamous cell histology
  • Clinical stage T1-2 N0, T2 N1, or M1 disease according to the 8th edition of AJCC
  • Loco-regionally recurrent head & neck cancer that has been previously treated with surgery, radiation therapy, and/or chemotherapy
  • Prior or concurrent primary malignancy (including second synchronous head & neck cancer) within the last 2 years of informed consent and whose natural history has the potential to interfere with the safety and efficacy assessment of the investigational agent
  • Ongoing or active infection requiring treatment with antimicrobial therapy within 2 weeks of randomization

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm AJNJ-90301900 (NBTXR3)JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33% of the Gross Tumor Volume.
Arm ACetuximabJNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33% of the Gross Tumor Volume.
Arm ARadiation TherapyJNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33% of the Gross Tumor Volume.
Arm BCetuximabInvestigator's choice of RT alone or RT in combination with cetuximab.
Arm BRadiation TherapyInvestigator's choice of RT alone or RT in combination with cetuximab.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Overall Survival (OS)48 months following first randomized participant

Time from randomization to death from any cause

Local-regional control48 months following first randomized participant

Time to local regional progression: time from Randomization to local-regional progression or death, whichever occurs first

Quality of Life over time - EQ 5D 5L48 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 - AEs48 months following first randomized participant

Adverse events (AEs)

Distant control48 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 Response48 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&N3548 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)

Trial Locations

Locations (166)

City of Hope

🇺🇸

Duarte, California, United States

Memorial Radiation Oncology Medical Group Laguna Hills

🇺🇸

Laguna Hills, California, United States

UCLA Hematology Oncology

🇺🇸

Los Angeles, California, United States

Hoag Memorial Hospital

🇺🇸

Newport Beach, California, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

Emory University Hospital Midtown

🇺🇸

Atlanta, Georgia, United States

Christus St. Vincent Regional Cancer Center

🇺🇸

Santa Fe, New Mexico, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

Herbert Irving Comprehensive Cancer Center Columbia University Medical Center

🇺🇸

New York, New York, United States

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City of Hope
🇺🇸Duarte, California, United States
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