[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"hpv-unrelated-head-and-neck-squamous-cell-carcinoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:hpv-unrelated-head-and-neck-squamous-cell-carcinoma":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,47],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":28,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100652731","phase-2-induction-pd-1-inhibitor-and-chemotherapy-followed-by-chemoradiotherapy-in-unresectable-or-inoperable-hpv-negative-la-hnscc-100652731",false,"NCT07776340","Induction PD-1 Inhibitor and Chemotherapy Followed by Chemoradiotherapy in Unresectable or Inoperable HPV-negative LA-HNSCC","Induction Chemoimmunotherapy Followed by Concurrent Chemoradiotherapy and Adjuvant Immunotherapy Versus Concurrent Chemoradiotherapy Alone in Unresectable or Inoperable Locoregionally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma: A Randomized, Controlled, Phase 2 Study","Inclusion Criteria:\n\n* Pathologically confirmed HPV-negative head and neck squamous cell carcinoma (including laryngeal, hypopharyngeal, or oropharyngeal cancer).\n* Loco-regionally advanced (Stage III-IVB) disease according to the 8th edition clinical staging system of the American Joint Committee on Cancer (AJCC)\u002FUnion for International Cancer Control (UICC).\n* Confirmed by a multidisciplinary team (MDT) as not amenable to curative surgery and deemed suitable for definitive concurrent chemoradiotherapy.\n\n\"Not amenable to curative surgery\" includes unresectable disease (anatomic impossibility of resection) or inoperable disease (patient medically unable to tolerate or declining surgical resection).\n\n* ECOG performance status of 0-1.\n* Pre-treatment neutrophils ≥ 1.5 × 10⁹\u002FL, hemoglobin ≥ 90 g\u002FL, platelets ≥ 100 × 10⁹\u002FL; total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT ≤ 1.5 × ULN, AST ≤ 1.5 × ULN, ALP ≤ 2.5 × ULN; creatinine ≤ 1.5 × ULN.\n* Activated partial thromboplastin time (APTT) and international normalized ratio (INR) ≤ 1.5 × ULN (patients on a stable dose of anticoagulant therapy, such as low molecular weight heparin or warfarin, with an INR within the therapeutic range for the anticoagulant, are eligible for screening).\n* Normal pulmonary and cardiac function.\n* Normal myocardial enzyme profile.\n* No prior radiotherapy, chemotherapy, immunotherapy, or biological targeted therapy, or any other antitumor treatment for the current tumor lesion(s).\n* Women of childbearing potential must have a negative pregnancy test (serum) within 7 days before enrollment and must voluntarily use appropriate contraception during the observation period and for 8 weeks after the last treatment; for men, they must be surgically sterile or agree to use appropriate contraception during the observation period and for 8 weeks after the last treatment.\n* Participants must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule.\n\nExclusion Criteria:\n\n* Has a history or presence of other malignancies, except for those that have been cured and with no evidence of disease for over 5 years (such as basal cell carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid carcinoma, etc.).\n* Has active autoimmune diseases or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); excluding autoimmune-mediated hypothyroidism stabilized with thyroid hormone replacement therapy; type I diabetes mellitus stabilized on insulin regimen; vitiligo or childhood asthma\u002Fallergies that have resolved and require no intervention in adulthood.\n* Has uncontrolled cardiac clinical symptoms or diseases, such as: (a) NYHA Class II or above heart failure; (b) unstable angina; (c) myocardial infarction within the past year; (d) clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention.\n* Has severe infection (CTCAE \\> Grade 2) within 4 weeks prior to the first dose of the study drug, active infection during screening, or unexplained fever \\> 38.5°C before administration (tumor-related fever may be considered for inclusion).\n* Has a history of allergy to any component of anti-PD-1 antibodies, paclitaxel-based drugs, or cisplatin.\n* Prior radiotherapy, chemotherapy, immunotherapy (including PD-1, anti-PD-L1 antibodies, anti-CTLA-4 antibodies, cancer vaccines, etc.), or biological targeted therapy for the current hypopharyngeal\u002Flaryngeal\u002Foropharyngeal cancer.\n* Concurrent participation in another clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study.\n* Requirement for systemic treatment with corticosteroids (prednisone equivalent dose \\> 10 mg\u002Fday) or other immunosuppressive agents within 2 weeks prior to the first dose of the study drug, except for topical use to manage local inflammation, prevent allergies, or manage nausea and vomiting. Other special cases should be discussed with the investigator. Inhaled or topical steroids and physiological doses of corticosteroid replacement for adrenal insufficiency (≤ 10 mg\u002Fday prednisone equivalent) are permitted in the absence of active autoimmune disease.\n* Major surgery or severe trauma within 4 weeks prior to the first dose of the study drug.\n* Has a history of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, or history of organ transplantation or allogeneic bone marrow transplantation.\n* Has a history of interstitial lung disease (excluding radiation pneumonitis not treated with steroids) or non-infectious pneumonitis.\n* Has a history or CT evidence of active tuberculosis infection, or history of active tuberculosis infection within 1 year prior to enrollment, or history of active tuberculosis infection more than 1 year ago without formal treatment.\n* Active hepatitis B (HBV DNA ≥ 2000 IU\u002FmL or 10⁴ copies\u002FmL) or hepatitis C (positive HCV antibody with HCV-RNA above the lower limit of detection of the assay).\n* Known history of drug abuse, alcohol abuse, or substance addiction\n* Pregnant or lactating women.\n* Other factors considered by the investigator that may lead to premature termination of the study, such as other severe diseases (including psychiatric disorders) requiring combined treatment, severely abnormal laboratory test values, family or social factors, or any other circumstances that may compromise subject safety or integrity of the study data.","ALL","18 Years","75 Years",{"count":20,"type":21},104,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","The goal of this clinical trial is to evaluate if adding chemotherapy and immunotherapy as induction treatment prior to definitive chemoradiotherapy could improve the outcomes of locally advanced HPV-negative head and neck squamous cell that are not amenable to surgery. The study aims to answer:\n\n1. Does this treatment improve the survival outcomes of participants?\n2. How do the tumors of participants response to the treatment?\n3. How is the safety of this treatment? Researchers will compare this treatment (induction chemoimmunotherapy, followed by concurrent chemoradiotherapy, and then immunotherapy as maintenance therapy) to concurrent chemoradiotherapy to see whether it provides additional clinical benefits.",[27],"HPV-unrelated Head and Neck Squamous Cell Carcinoma",[29,30,31,32,33],"Head and Neck Squamous Cell Carcinoma","Programmed Cell Death Receptor 1 (PD-1)","Chemotherapy","Chemoradiotherapy","Induction Treatment","NOT_YET_RECRUITING","2026-08-19",{"date":37,"type":38},"2026-08-20","ACTUAL",{"date":40,"type":21},"2026-09-01",{"date":42,"type":21},"2030-03",{"name":44,"class":45},"Fudan University","OTHER",1,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":54,"targetDuration":4,"studyType":22,"phases":56,"briefSummary":58,"conditions":59,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":70},"100436685","phase-3-palbociclib-and-cetuximab-versus-cetuximab-monotherapy-for-patients-with-cdkn2a-altered-hpv-unrelated-head-and-neck-squamous-cell-carcinoma-who-experienced-disease-progression-on-a-pd-1l1-inhibitor-100436685","NCT04966481","Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1\u002FL1 Inhibitor","Palbociclib and Cetuximab Versus Cetuximab Monotherapy for Patients With CDKN2A-altered, HPV-unrelated Head and Neck Squamous Cell Carcinoma Who Experienced Disease Progression on a PD-1\u002FL1 Inhibitor: A Multicenter, Open-Label, Randomized Phase 3 Trial","Inclusion Criteria:\n\n* Histologically or cytologically confirmed RM-HNSCC that is HPV-unrelated disease; defined as SCC of the oral cavity, larynx, or hypopharynx and p16 negative SCC of the oropharynx or p16 negative non-cutaneous SCC unknown primary of the neck.\n* CDKN2A loss-of-function (LOF) alteration: mutation or homozygous deletion described on genomic sequencing report.\n* Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam, per RECIST 1.1.\n* Disease progression on a PD-1\u002FL1 inhibitor-containing regimen (given as monotherapy or in combination with other therapy).\n* Received no more than three lines of prior therapy for RM-HNSCC.\n* At least 18 years of age.\n* ECOG performance status ≤ 1.\n* Normal bone marrow and organ function as defined below:\n\n  * Hemoglobin ≥ 8 g\u002FL\n  * Absolute neutrophil count ≥ 1,000\u002Fmcl\n  * Platelets ≥ 100,000\u002Fmcl\n  * Total bilirubin ≤ 3 x institutional upper limit of normal (IULN)\n  * AST(SGOT)\u002FALT(SGPT) ≤ 5 x IULN (for cases involving liver metastases, AST\u002FALT ≤ 10 x IULN)\n  * Serum creatinine \\\u003C 3 x IULN or creatinine clearance \\> 30 mL\u002Fmin by Cockcroft-Gault\n* The effects of palbociclib and cetuximab on the developing human fetus are unknown. For this reason and because CDK 4\u002F6 inhibitors are known to be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and 3 months days after completion of the study\n* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).\n\nExclusion Criteria:\n\n* Prior treatment with cetuximab for recurrent or metastatic disease (however, prior cetuximab given as a component of multimodality therapy for newly diagnosed, locally advanced, non-metastatic HNSCC is allowable).\n* Prior treatment with a CDK4\u002F6 inhibitor for RM-HNSCC.\n* Rb (retinoblastoma) loss: mutation or homozygous deletion described on genomic sequencing report.\n* Currently receiving any other investigational agents.\n* A history of other malignancy with the exception of malignancies for which all treatment was completed at least 1 year before registration and the patient has no evidence of recurrent\u002Fpersistent disease.\n* Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period\n* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in the study (excluding cetuximab).\n* Prior grade 3 or 4 (per CTCAE 5.0) hypersensitivity reaction to cetuximab.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.\n* QTc \\>500 msec (using Bazette formula).\n* Patients with HIV are eligible unless their CD4+ T-cell counts are \\\u003C 350 cells\u002FmcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended. Recommend exclusion of specific ART agents based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates, concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers (efavirenz) should be contraindicated).",{"count":55,"type":21},81,[57],"PHASE3","This multicenter, open-label, randomized phase 3 trial will determine if palbociclib and cetuximab (Arm 1) improves overall survival (OS) in comparison to cetuximab monotherapy (Arm 2) in patients with CDKN2A-altered, HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on a PD-1\u002FL1 inhibitor (given as monotherapy or in combination with other therapy).",[27],"RECRUITING","2026-05-15",{"date":63,"type":38},"2026-05-19",{"date":65,"type":38},"2022-04-06",{"date":67,"type":21},"2028-02-28",{"name":69,"class":45},"Washington University School of Medicine",5]