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NCT02764593 · CITED IN SOURCE DOCUMENTS

Safety Testing of Adding Nivolumab to Chemotherapy in Patients With Intermediate and High-Risk Local-Regionally Advanced Head and Neck Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1
Status at capture
COMPLETED
Registry last update
2022-11-29

This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx. * Intermediate-risk group: Oropharynx cancer that is p16-positive by immunohistochemistry with smoking status \> 10 Pack-years, stage T1-2N2b-N3 OR ≤ 10 pack-years, stage T4N0-N3 or T1-3N3. * High-risk group: Oral cavity, larynx, hypopharynx, or p16-negative oropharynx cancer, stage T1-2N2a-N3 or T3-4-N0-3 based on the following diagnostic workup: * Mandatory submission of H\&E and p16 stained slides for central review of p16 staining is required for oropharyngeal patients and H\&E stained slide block (or punch biopsy of paraffin block) for PD-L1 expression analysis for all patients * History/physical examination within 28 days prior to registration * Examination by Radiation Oncologist, Medical Oncologist, and Ear, Nose, Throat (ENT) or Head \& Neck Surgeon within 28 days prior to registration * Fiberoptic exam with laryngopharyngoscopy within 28 days prior to registration * Diagnostic quality, cross sectional imaging of the thorax within 28 days prior to registration; 18-F-FDG-PET/CT or conventional CT are acceptable. * Diagnostic quality CT or MRI of neck, with contrast, within 28 days prior to registration; a 18-F-FDG-PET/CT of the neck only is acceptable as a substitute if the CT is of diagnostic quality and with IV contrast. * Age ≥ 18 years * The trial is open to both genders Exclusion Criteria: * Definitive clinical or radiologic evidence of distant (beyond cervical lymph node and neck tissue) metastatic disease. * Patients with oral cavity cancer are excluded from participation if resection of the primary tumor is considered technically feasible by an oral or head and neck cancers surgical subspecialist. * Carcinoma of the neck of unknown primary site origin (even if p16-positive). * Absence of RECIST, v. 1.1 defined measurable disease. * Gross total excision of both primary and nodal disease; this includes tonsillectomy, local excision of primary site, and nodal excision that removes all clinically and radiographically evident disease. Patients with RECIST, v. 1.1 evaluable remaining cancer either in the neck or primary site remain eligible. * Simultaneous primary cancers or separate bilateral primary tumor sites. * Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible). * Prior systemic chemotherapy for the study cancer. * Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields. * Patients with active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism and psoriasis. * Use of systemic corticosteroids (\> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration, with exception of inhaled or topical steroids. * Known immunosuppressive disease, for example HIV infection or history of bone marrow transplant or chronic lymphocytic leukemia (CLL).
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cisplatin will be given weekly. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
    intervention Names
    1. Drug: Nivolumab
    2. Drug: Cisplatin
    3. Radiation: IMRT
    label
    Arm 1 (Nivolumab + Cisplatin)
    type
    EXPERIMENTAL
  2. description
    Patients will receive Nivolumab via IV administration starting 14 days prior to IMRT, then Day 1 of IMRT and then every 21 days for 6 doses. Cisplatin will be given every 21 days for 3 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
    intervention Names
    1. Drug: Nivolumab
    2. Drug: Cisplatin
    3. Radiation: IMRT
    label
    Arm 2 (Nivolumab + High-dose Cisplatin)
    type
    EXPERIMENTAL
  3. description
    Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. Cetuximab will be given for 7 doses. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
    intervention Names
    1. Drug: Nivolumab
    2. Drug: Cetuximab
    3. Radiation: IMRT
    label
    Arm 3 (Nivolumab + Cetuximab)
    type
    EXPERIMENTAL
  4. description
    Patients will receive Nivolumab via IV administration every 14 days for 10 doses starting 14 days prior to IMRT. IMRT will be given at 5 fractions per week for 7 weeks for a dose of 70 Gy. Adjuvant nivolumab every 28 days for 7 doses will be administered starting 3 months after end of chemoradiation. Adjuvant administration of nivolumab may be discontinued if more than 4 of first 8 patients receive less than 7 doses.
    intervention Names
    1. Drug: Nivolumab
    2. Radiation: IMRT
    label
    Arm 4 (Nivolumab + IMRT)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm 1 (Nivolumab + Cisplatin)
    2. Arm 2 (Nivolumab + High-dose Cisplatin)
    3. Arm 3 (Nivolumab + Cetuximab)
    4. Arm 4 (Nivolumab + IMRT)
    description
    Anti-PD-1 targeted immunotherapy
    name
    Nivolumab
    other Names
    1. Opdivo
    type
    DRUG
  2. arm Group Labels
    1. Arm 1 (Nivolumab + Cisplatin)
    2. Arm 2 (Nivolumab + High-dose Cisplatin)
    description
    Anti-cancer alkylating agent
    name
    Cisplatin
    other Names
    1. Platinol
    type
    DRUG
  3. arm Group Labels
    1. Arm 3 (Nivolumab + Cetuximab)
    description
    Epidermal Growth Factor Receptor (EGFR) antagonist
    name
    Cetuximab
    other Names
    1. Erbitux
    type
    DRUG
  4. arm Group Labels
    1. Arm 1 (Nivolumab + Cisplatin)
    2. Arm 2 (Nivolumab + High-dose Cisplatin)
    3. Arm 3 (Nivolumab + Cetuximab)
    4. Arm 4 (Nivolumab + IMRT)
    description
    High-precision radiotherapy
    name
    IMRT
    other Names
    1. Intensity Modulated Radiation Therapy
    type
    RADIATION
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
40
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    A nivolumab attributable, dose-limiting toxicity (DLT) will be defined as follows: 1\) Any ≥ grade 3 adverse event (CTCAE, v. 4) that is related to nivolumab that does not resolve to grade 1 or less within 28 days; 2) A delay in radiotherapy of \> 2 weeks due to toxicity related to nivolumab; 3) Inability to complete radiotherapy due to toxicity related to nivolumab; 4) Inability to receive an adequate dose (≥ 70%) of cisplatin (Arm 1 and 2) or cetuximab (Arm 3) due to toxicity definitely related to nivolumab.
    measure
    Dose Limiting Toxicity (DLT)
    time Frame
    From the first dose of nivolumab to 28 days after the completion of radiation therapy.
Full study description
brief Summary
This study will evaluate the safety of adding nivolumab to several chemotherapy platforms with weekly cisplatin, high-dose cisplatin, cetuximab or radiation therapy alone.
Source references
references
  1. citation
    Gillison ML, Ferris RL, Harris J, Colevas AD, Mell LK, Kong C, Jordan RC, Moore KL, Truong MT, Kirsch C, Chakravarti A, Blakaj DM, Clump DA, Ohr JP, Deeken JF, Gensheimer MF, Saba NF, Dorth JA, Rosenthal DI, Leidner RS, Kimple RJ, Machtay M, Curran WJ Jr, Torres-Saavedra P, Le QT. Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):847-860. doi: 10.1016/j.ijrobp.2022.10.008. Epub 2022 Oct 11.
    pmid
    36228746
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      1. context exact
        rapy followed by concurrent chemoradiation therapy</a>.</li><li>Chemoradiation therapy with immunotherapy (under clinical evaluation). <a href="/clinicaltrials/NCT02764593">RTOG 3504</a> (NCT02764593) evaluated concurrent chemoradiation therapy with nivolumab in patients with intermediate- to high-risk head and neck cancer. </li>
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      2. context exact
        chemoradiation therapy</a>.</li><li>Chemoradiation therapy with immunotherapy (under clinical evaluation). <a href="/clinicaltrials/NCT02764593">RTOG 3504</a> (NCT02764593) evaluated concurrent chemoradiation therapy with nivolumab in patients with intermediate- to high-risk head and neck cancer. </li><li> Treatment de-intensific
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      source retrieved at
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      source title
      Oropharyngeal Cancer Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: May 14, 2025
        datetime
        2025-05-14T12:00:00Z
        display
        May 14, 2025

    Preserved source evidence · Not medical advice