Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified [NOS]) of the head/neck (oral cavity, oropharynx, hypopharynx or larynx); pathologic stage III or IVA (American Joint Committee on Cancer [AJCC] 8): T3-T4a, N0-3, M0 or T1-T2, N1-3, M0
Primary tumor site: oral cavity, oropharynx, larynx, hypopharynx
Patients must have histologically or cytologically confirmed squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx or larynx; patients eligible for inclusion must have stage III-IV SCC of the above sites based on current American Joint Committee on Cancer (AJCC) clinical and imaging based staging; only patients with human papillomavirus (HPV)- disease will be included in the phase II portion of the study; HPV status will be ascertained using the currently utilized clinical standard of p16 overexpression via immunohistochemistry
Patients may not have been treated for another SCC of the oral cavity, oropharynx, hypopharynx or larynx in the past
Must have diagnosis of head and neck squamous cell carcinoma of the oropharynx (tonsil, base of tongue, soft palate, or oropharyngeal walls), hypopharynx, or larynx
Histologically or cytologically confirmed incurable HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, and/or level 1-3 neck node with non-skin squamous cell carcinoma (SCC) and unknown primary; “incurable” is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection)
Subject must have histologically or cytologically confirmed locoregionally recurrent squamous cell carcinoma of the head and neck (including any primary site, such as oral cavity, oropharynx, larynx or hypopharynx, and nasopharynx carcinoma)
Any stage HNSCC of the 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx, 5) nasal cavity/paranasal sinuses, 6) unknown primary; patients with resectable or recurrent disease that is amenable to surgery are eligible
Biopsy-proven squamous cell carcinoma of the oral cavity or oropharynx without distant organ metastases
Tumors of the lips, sinuses, salivary glands, nasopharynx, hypopharynx, or larynx
Participants with previously untreated T1/T2 N0 squamous cell carcinoma of the oral cavity with or without extension to the oropharynx
Patient has pathologically confirmed SCCHN (oral cavity, oropharynx, larynx, hypopharynx) with evidence of local and/or locoregional recurrence; laryngeal tumors will only be included if there is evidence of extralaryngeal spread, or there is associated nodal disease; for all other sites, superficial tumors can only be included if there is associated nodal disease
Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
ARM 2 - A: Presence of disease at the oropharynx, hypopharynx, or larynx sub-sites
Histologically or cytologically confirmed stage III or IV HNSCC oral cavity, hypopharynx, oropharynx, larynx (excluding p16 or human papillomavirus [HPV]-positive oropharynx primaries and sinonasal primaries)
Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no evidence of distant metastasis; biopsy sampling of primary tumor with pathology report documenting diagnostic tissue type is required
Histologically confirmed squamous cell carcinoma of the head and neck, including the following subtypes: oral cavity, oropharynx, hypopharynx, larynx.
Larynx squamous cell carcinoma (SCC), hypopharynx SCC, or oral cavity SCC; HPV-unrelated oropharyngeal squamous cell carcinoma (OPSCC) (defined as p16^INK4a negative by immunohistochemistry [IHC] [staining in < 70% of cells] or HPV high risk [type 16 or 18] negative by in situ hybridization [ISH]); P16^INK4a positive larynx SCC, hypopharynx SCC, and oral cavity SCC are eligible
Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx & larynx) that is not amenable to curative therapy.
p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity
Patients must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx; squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive
Previous radiation treatment for head and neck mucosal primary cancers within the past 5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity).
Cancers considered to be from an oral cavity site (oral tongue, floor of mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive
Primary tumors of any head and neck (oral cavity, oropharynx, hypopharynx, or larynx) site will be included
Histologically or cytologically proven squamous cell carcinoma of the head and neck (lip, oral cavity, oropharynx, larynx, hypopharynx, non- Epstein–Barr virus [EBV] related nasopharynx, sinonasal, cutaneous), not amenable to curative intent therapy
Synchronous primaries outside of the oropharynx and larynx
Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy); patients who refuse radical resection are eligible
Pathologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, larynx, hypopharynx, or oral cavity with clinical or pathologic high-risk features for whom cisplatin and radiation would be considered appropriate care.
Patients must have histologically-confirmed head and neck squamous cell carcinoma with no evidence of distant metastasis; the primary site may be the oral cavity, oropharynx, larynx, or hypopharynx; patients with squamous cell carcinoma of unknown primary, metastatic to cervical lymph nodes, are permitted to enroll
Have histologically or cytologically-confirmed head and neck squamous cell carcinoma of the oral cavity (excluding lip), oropharynx, hypopharynx, or larynx.
Biopsy proven HNSCC of the oropharynx, larynx, hypopharynx, or oral cavity stage III-IVB as defined by American Joint Committee on Cancer (AJCC) T0 - T4, N0 - N3, M0
Histologically or cytologically confirmed incurable HNSCC of the oral cavity, oropharynx, larynx, hypopharynx, and/or level 1-3 neck node with non-cutaneous squamous cell carcinoma (SCC) and unknown primary; “incurable” is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection)
T1/2N0-2M0 SCC of the oropharynx, hypopharynx or larynx
Recurrence of previously pathologically proven squamous cell carcinoma of the head and neck, including original primary sites in the paranasal sinuses, nasal cavity, nasopharynx, oropharynx, oral cavity, larynx, hypopharynx, salivary glands, and/or involvement of cervical lymph nodes
Patients must have pathologically confirmed, previously untreated, resectable, squamous cell carcinoma of the larynx or hypopharynx
Additional inclusion for Part B:Has histologically and/or cytologically confirmed SCCHN that is RM and not amendable to curative therapy by surgery or radiation. Squamous cell carcinoma of the head and neck originating from the following sites is eligible: oral cavity, oropharynx, larynx, or hypopharynx. Has at least 1 SCCHN tumour lesion (TL) amenable to biopsy and must have failed, refused, or has been found to be ineligible for least 1 prior platinum-based chemotherapy for RM-SCCHN Additional inclusion criteria for Arms B1 & B2:must have had prior exposure to anti PDL-1 antibody
Histological or cytological documentation of squamous cell carcinoma of the head and neck (SCCHN) (oral cavity, oropharynx, hypopharynx, or larynx) that is recurrent, locally advanced, or metastatic and is not amenable to curative treatment options, surgery or definitive chemoradiation therapy.
Pathologically-confirmed squamous cell carcinoma of the oral cavity, oropharynx or hypopharynx or HPV-positive unknown primaries presumed to be of oropharyngeal origin
Pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx or nasopharynx
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Pathologically confirmed (histology or cytology) stage III or IVA squamous cell cancer of the oral cavity (excluding lip)
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Hemoglobin > 9 g/dL
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Lymphocyte count > 500 x 10^9/mL
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Neutrophil count > 1500 × 10^9/mL
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Platelet count > 100,000 x 10^9/mL
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Serum albumin > 3.0 g/dL
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Willing and able to give informed consent and adhere to protocol therapy
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any medical contraindications or previous therapy that would preclude treatment with either nivolumab, IRX-2, the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Clinical status of either subject or tumor such that administration of 10 day neoadjuvant IRX-2 1 or 2 before surgery would be medically inappropriate
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Primary tumor of the oropharynx
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Any investigational agent within the previous 30 days
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Myocardial infarction within the last 3 months
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Evidence of distant metastases (M1 disease) or other concurrent primary malignancy
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Stroke or other symptoms of cerebral vascular insufficiency within the last 3 months
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Allergy to ciprofloxacin (or other quinolones), acetylsalicylic acid
ORAL CAVITY SQUAMOUS CELL CARCINOMA COHORT: Prior axillary dissection
The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, paranasal sinuses, hypopharynx, or larynx; squamous cell carcinoma of unknown primary in cervical lymph node can be included only if human papillomavirus (HPV) status is positive
Histologically confirmed squamous cell carcinoma of the head and neck including the oral cavity, oropharynx, hypopharynx or larynx, excluding nasopharynx
Histologically or cytologically-confirmed diagnosis of HNSCC of the oral cavity, oropharynx, larynx, or hypopharynx.
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:
Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), hypopharynx or larynx
Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
Stage IVA-B disease of 1) oral cavity, 2) oropharynx, 3) larynx, 4) hypopharynx
Histologically proven squamous cell carcinoma of the oropharynx, hypopharynx or larynx
Patients must have a histologically or cytologically confirmed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
Patients must have histologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or poorly differentiated carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx with no evidence of distant metastasis; biopsy sampling of primary tumor with pathology report documentation of confirmed diagnostic tissue type is required; patients should be evaluated by a radiation oncologist, medical oncologist and otolaryngologist prior to enrolling on study
Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16 positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas
American Joint Committee on Cancer (AJCC) stage III/IVB, excluding T1N1, histologically or cytologically confirmed squamous cell carcinoma or undifferentiated carcinoma of the head and neck; patients should not have distant metastasis; primary sites include: oropharynx, hypopharynx, larynx
Histologically or cytologically confirmed (from the primary lesion and/or regional lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, or larynx that has not been previously treated or resected; patients with unresectable oral cavity cancers are also eligible; human papilloma virus (HPV) testing is required, although both HPV-positive and -negative patients are eligible
Patients must have pathologically-confirmed, previously untreated, clinically accessible (without general anesthesia) locally advanced squamous cell carcinoma of the larynx, hypopharynx, oropharynx, or oral cavity or nonresectable head and neck squamous cell carcinomas of the skin
Previous radiation treatment for head and neck mucosal primary cancers within the past 5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity)
Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx.
Pathologically (histologically) proven diagnosis of squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified [NOS], etc.) of the head/neck (oral cavity, oropharynx or larynx); note: hypopharynx primaries are excluded
Documented evidence of recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx).
Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.
Patients must have histologically or cytologically confirmed diagnosis (from primary lesion and/or lymph nodes) of Squamous Cell Cancer of the oropharynx, hypopharynx or larynx (For patients with oropharynx primary, the tumor must be negative for p16 by immunohistochemistry).
Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology)
Histologically- or cytologically-confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
Histologically or cytologically documented squamous cell carcinoma of the oropharynx, larynx or hypopharynx; human papillomavirus (HPV) status will not be assessed for eligibility
Clinical diagnosis of squamous cell cancer of the head and neck (non-nasopharynx primary tumors: oral cavity, oropharynx, hypopharynx and larynx) or skin
Previously untreated, histologically proven primary squamous cell carcinoma arising in the oral cavity, oropharynx, or supraglottic larynx, and amenable to transoral approach; NOTE: in some cases, patients with disease deemed amenable to transoral approach at the time of diagnosis may have their entire primary tumor extirpated via diagnostic biopsy; when this happens, patients will remain eligible for the protocol as long as they have evaluable disease in the neck; in this case, the choice between a transoral procedure plus dissection or neck dissection alone will be made by the surgeon as per standard of care
Patients with pathologically confirmed cancers of paranasal sinuses, oropharynx, oral cavity, nasopharynx, larynx, hypopharynx, and unknown primary and will receive definitive radiation therapy with or without chemotherapy
Histologically confirmed metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, hypopharynx or larynx; metastatic or recurrent lesions of the nasopharynx and sinus are excluded
Primary sites other than oral cavity, oropharynx, hypopharynx, and larynx
Patients must have cytologically or histologically proven recurrent or metastatic squamous cell cancer of the head and neck (SCCHN) from the primary tumor or lymph nodes of the oral cavity, larynx, oropharynx, or hypopharynx.
Histologically confirmed squamous cell carcinoma of the head and neck (SCCHN), from any of the following primary sites only: oral cavity, oropharynx, hypopharynx, and larynx.
Confirmed squamous cell carcinoma of the head and neck (oropharynx, oral cavity, hypopharynx, or larynx) or skin
Patients must have pathologically-confirmed, resectable, squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx
Advanced stage but not metastatic SCC of the oral cavity (III or IVa, b); sites in the oral cavity include oral tongue, floor of mouth, hard palate, gingiva, buccal mucosa, retromolar trigone; often, head & neck tumors may involve other adjacent sites, such as the oropharynx- in these cases, the criteria is that the tumor must appear to have originated in the oral cavity per ear, nose, and throat (ENT)/radiation oncology
Patients must have histologically or cytologically confirmed SCCHN that is recurrent and/or metastatic and not amendable to curative therapy by surgery or radiation; SCCHN originating from the following sites are eligible: oral cavity, oropharynx, larynx, hypopharynx and paranasal sinus; for patients with a diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved by the principal investigator
Histologically confirmed recurrent squamous cell carcinoma of the oral cavity, pharynx, (oropharynx, larynx) and neck
Histologically or cytologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck (oral cavity, oropharynx, hypopharynx or larynx) that is incurable by local therapy.
Histologically or cytologically confirmed primary, untreated SCCHN including variants. Patients must be candidates for surgical resection. Primary tumors of oral cavity, oropharynx, hypopharnyx or larynx are included.
Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included
Histologically confirmed R/M SCCHN of mucosal origin (e.g., oral cavity, oropharynx, hypopharynx, larynx) that is not amenable to further curative local therapy (e.g., surgery, radiation including re-irradiation) (1L R/M)
Head and neck squamous cell carcinoma (HNSCC) Cohort: Participants with histologically confirmed inoperable, locally advanced or metastatic, recurrent, or persistent HNSCC (oral cavity, oropharynx, hypopharnyx, or larynx) not amenable to curative therapy not previously treated with anti-PD-L1/PD-1 and/or anti-CTLA-4 (investigational or approved)
Histologically or cytologically confirmed R/M HNSCC of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy
Histologically confirmed SCCHN from any of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx.
Patients with Tl/T2 squamous cell carcinoma of the oral cavity with or without extension to the oropharynx
Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease. Participants with multiple synchronous tumors are not eligible for the study.
Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
Histologically confirmed locally advanced cancer of mucosa of the head and neck.\r\n* Eligible subsites will include nasal cavity, paranasal sinuses, nasopharynx, oropharynx, oral cavity, major salivary glands, oropharynx, larynx, hypopharynx, cervical esophagus, or unknown primary site with lymph node metastases.\r\n* Clinical or pathologic stage III-IV
Has a new or recurrent American Joint Committee on Cancer (AJCC) stage I-IV squamous cell carcinoma of the upper aerodigestive tract (including lip/oral cavity, nasopharynx, salivary gland, oropharynx, hypopharynx, paranasal sinus, and larynx cancers)
Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck, defined as SCC of the oral cavity or oropharynx that will be treated with cisplatin plus concurrent IMRT Note: Patients with unknown primary tumors whose treatment plan matches the requirements specified in Inclusion Criteria #2 and #3 below are eligible for the trial.
Tumor of the lips, larynx, hypopharynx, nasopharynx, sinuses, or salivary glands
Family member or friend of an adult patient with a new diagnosis of stage II-IV cancers of the tongue, gum, oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, or parotid who is receiving radiation therapy for curative intent
Patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx will be eligible
Histological confirmation of tumor of the oral cavity, oropharynx, supraglottic larynx, or nasopharynx
Have recently diagnosed (within previous 6 months) pathologically confirmed, non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx that will be treated with CRT therapy as first line non-surgical treatment. Scans (CT, PET, and/or MRI) obtained within 120 days prior to consent for screening can be used to determine the subject's eligibility.
Subjects undergoing definitive mucosal head and neck tumor resection including oral cavity, oropharynx, larynx, and hypopharynx
Pathologically-confirmed diagnosis of squamous cell carcinoma of the head and neck (SCCHN), defined as SCC of the oral cavity or oropharynx, that will be treated with standard cisplatin and Intensity-Modulated Radiation Therapy (IMRT)
Histologic proof of squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx
Patients must have histologically or cytologically confirmed squamous cell carcinoma of the nasopharynx, oropharynx, larynx, hypopharynx, oral cavity
Eligible tumor and premalignant lesion sites include oral cavity (buccal mucosal, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, larynx (glottis, supraglottis, subglottis, epiglottis), hypopharynx paranasal sinus and nasal cavity
Lesion sites include oral cavity (buccal mucosa, gingival, floor of mouth, dorsal/ventral tongue, pharyngeal wall), oropharynx, hypopharynx, larynx (glottis, supraglottis, subglottis, epiglottis), nasopharynx and paranasal sinuses
Biopsy-proven HNC including cancers of the nasopharynx, oropharynx, larynx, hypopharynx, or HNC of unknown primary origin amenable to therapy with radiation and concurrent chemotherapy
Patients with oral cavity squamous cell cancer requiring neck dissection
Histologically proven squamous cell carcinoma of the head and neck (SCCHN) from one of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx
Recently-diagnosed (within the last 6 months), histologically-documented, non-metastatic squamous cell carcinoma of the oral cavity and/or oropharynx amenable to radiotherapy with concurrent chemotherapy as the definitive treatment modality.
Histologically or cytologically proven squamous cell carcinoma of the oral cavity or pharynx (OSCC)
locoregional OSCC (T stage II-IV) of the oral cavity, oropharynx, larynx, or hypopharynx without evidence of distant metastases
Histologically confirmed diagnosis of metastatic or recurrent SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx. Disease must be unsuitable for curative surgical resection and must not be amenable to curative radiotherapy.
Histologically or cytologically-confirmed, HPV (+) or HPV (-) squamous cell carcinoma of the nasopharynx (WHO Type 1), oropharynx, hypopharynx, larynx (supraglottis, glottis, subglottis) or oral cavity,