HPV-positive oropharyngeal squamous cell carcinoma
Conditions
Interventions
Arm B (Standard Concurrent Chemoradiotherapy Control Group):Concurrent chemoradiotherapy
Arm A (Combined Therapy Group):Induction Chemotherapy + Immunotherapy+Concurrent chemoradiotherapy+Maintenance immunotherapy
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Treatment-naive patients with HPV-positive oropharyngeal cancer; according to the 9th edition of AJCC/UICC staging system: clinical stage cT1-4N2-3M0 with radiologically confirmed positive lymph node iENE. 2. Definite pathological diagnosis of HPV-associated squamous cell carcinoma via oropharyngeal biopsy; immunohistochemical staining positive for p16, and positive expression of high-risk HPV subtypes. 3. Age: 18-75 years old. 4. ECOG performance status score of 0-1. 5. Pre-treatment hematological and biochemical indexes: (1) Neutrophil count >= 1.5 x 10^9/L, hemoglobin >= 90 g/L, platelet count >= 100 x 10^9/L; (2) Total bilirubin <= 1.5 x upper limit of normal (ULN), ALT <= 1.5 x ULN, AST <= 1.5 x ULN, ALP <= 2.5 x ULN; (3) Serum creatinine <= 1.5 x ULN. 6. Activated partial thromboplastin time (APTT) and international normalized ratio (INR) <= 1.5 x ULN. Patients on stable-dose anticoagulation therapy (e.g., low molecular weight heparin or warfarin) with INR within the expected therapeutic range of anticoagulants are eligible for screening. 7. Pulmonary function, cardiac function and myocardial enzyme spectrum within normal reference ranges. 8. No prior receipt of any anti-tumor therapy targeting the lesion, including radiotherapy, chemotherapy, immunotherapy or targeted biologic therapy. 9. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and agree to use reliable contraception throughout the study period. Male participants must practice effective contraception from the start of treatment until 120 days after the last study drug administration; male participants must agree to use effective contraceptive measures from study initiation until at least 6 months after study drug discontinuation. 10.Voluntarily sign the informed consent form and be willing to complete the study per protocol requirements.
Exclusion criteria
Exclusion criteria: 1.History of or concurrent other malignant tumors, except for malignancies cured with disease-free survival longer than 5 years, such as basal cell carcinoma of the skin, cervical carcinoma in situ, and papillary thyroid carcinoma. 2.Active autoimmune diseases or history of autoimmune diseases (including but not limited to interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Exceptions include: autoimmune hypothyroidism maintained on stable-dose thyroid replacement hormone; type 1 diabetes controlled with stable-dose insulin; vitiligo; or resolved childhood asthma/allergy requiring no intervention in adulthood. 3.History of clinically significant liver diseases, such as hepatitis C (positive hepatitis C antibody); chronic active hepatitis B (HBsAg positive for more than 6 months, HBV DNA = 2000 IU/mL, ALT = 2 × ULN, excluding hepatitis caused by drugs or other etiologies); alcoholic hepatitis, non-alcoholic steatohepatitis, prior hepatectomy, liver cirrhosis, etc. 4.History of immunodeficiency diseases, including positive HIV test, other acquired or congenital immunodeficiency disorders, history of solid organ transplantation or allogeneic bone marrow transplantation. 5.History of allergy to any component of anti-PD-1 antibodies, taxane drugs, or cisplatin. 6.Impaired cardiac function or clinically significant cardiac diseases, including but not limited to any of the following: baseline Fridericia-corrected QT interval > 450 ms or congenital long QT syndrome; concomitant diseases that may prolong the QT interval as assessed by the investigator, such as autonomic neuropathy (secondary to diabetes or Parkinson’s disease), HIV infection, liver cirrhosis, uncontrolled hypothyroidism, heart failure; history of severe uncontrolled arrhythmia; history of myocardial infarction, unstable angina, coronary artery bypass grafting, NYHA class II or above heart failure, cerebrovascular accident or transient ischemic attack within 3 months prior to first study drug administration; clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention. 7.Presence of any severe and/or uncontrolled medical condition or other circumstances that, in the judgment of the investigator and sponsor, may interfere with the patient’s participation in the study, including but not limited to: uncontrolled diseases whose management may be affected by study participation; history of severe skin diseases receiving targeted therapy; history of interstitial lung disease (excluding radiation pneumonitis without hormone treatment), non-infectious pneumonia, severe chronic obstructive pulmonary disease, obstructive lung disease, severe pulmonary insufficiency, symptomatic bronchospasm; life-threatening autoimmune or ischemic diseases. 8.Severe infection (CTC AE grade > 2) within 4 weeks prior to first study drug administration; active infection during screening; unexplained fever > 38.5 ? before dosing (tumor-related fever is allowed for enrollment). 9.Prior receipt of any therapy for HPV-positive oropharyngeal cancer, including radiotherapy, chemotherapy, immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies, tumor vaccines, etc.), targeted biologic therapy, participation in other clinical trials, or other anti-tumor treatments. 10.Concurrent enrollment in another clinical study, except for observational (non-interventional) studies or follow-up of interventional clini
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-Free Survival (EFS); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival;Locoregional Recurrence?free Survival;Progression Free Survival;Distant Metastasis?free Survival;Adverse Events; | — |
Countries
China
Contacts
Public ContactLu Xueguan
Fudan University Shanghai Cancer Center
Outcome results
None listed