Efficacy and Safety of Immunotherapy Combined With Neoadjuvant Chemotherapy in Patients With Locally Advanced HPV (-) Head and Neck Squamous Cell Carcinoma: a Phase II Clinical Trial

This is an interventional treatment trial for Efficacy and Safety of Immunotherapy Combined With Neoadjuvant Chemotherapy in Patients With Locally Advanced HPV (-) HNSCC Read More

Inclusion Criteria: 1. The patients voluntarily participated in the clinical trial and signed the informed consent; 2. Histologically and pathologically confirmed locally advanced (stage Ⅲ - Ⅳ b) and HPV (-) head and neck squamous cell carcinoma. The primary tumor sites included oral cavity, oropharynx, larynx and hypopharynx; 3. The newly diagnosed patients did not receive any anti-tumor treatment ; 4. At least one measurable lesion (RECIST v1.1); 5. PS score was 0-1; 6. The main organ function met the following criteria within 7 days before treatment ① Blood routine examination standard (without blood transfusion within 14 days) Hemoglobin (HB) ≥ 90g / L; Absolute neutrophil count (ANC) ≥ 1.5 × 10*9/L；Platelet count (PLT) ≥ 80 × 10*9/L；② Biochemical test standard: Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN; Serum creatinine (CR) ≤ 1.5 ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; ③ Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ the lower limit of normal value (50%); 7. Women of childbearing age should agree to use contraceptive measures (such as intrauterine device, contraceptive or condom) during the study period and within 6 months after the end of the study; Serum or urine pregnancy test was negative within 7 days before study enrollment. Male patients should agree to use contraception during the study period and within 6 months after the end of the study period.

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Exclusion Criteria: 1) Patients with carcinoma of nasal cavity and paranasal sinuses, nasopharyngeal carcinoma and HPV (+) oropharyngeal carcinoma;

2) Patients who have used immune checkpoint inhibitors (including PD-1, PD-L1, PD-L2 and CTLA-4 inhibitors) in the past;

3) At the same time, there were other malignant tumors which were not controlled or under treatment;

4) Patients with any severe and / or uncontrolled medical disease include:

• The patients who used at least two kinds of antihypertensive drugs still had poor blood pressure control (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 100 mmHg);

  • Grade 1 or above myocardial ischemia or myocardial infarction and grade 2 or above congestive heart failure (NYHA classification);

    • Sinus bradycardia; Or second degree or more atrioventricular block, or sinus arrest (except pacemaker installed); Arrhythmia (including QTc ≥ 480ms); It is necessary to use drugs known to prolong QTc interval, including antiarrhythmic therapy;

      • Active or uncontrolled severe infection (≥ CTC AE grade 2 infection);

        • Patients with liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need antiviral drugs;

          ⑥ Renal failure requiring hemodialysis or peritoneal dialysis;

          ⑦ History of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or organ transplantation;

          ⑧ The patients with diabetes had poor blood glucose control (FBG > 10mmol / L);

          • Urine routine examination showed that urine protein was ≥ + +, and 24-hour urine protein was more than 1.0g;

            5) Patients who received major surgical treatment, open biopsy or obvious traumatic injury within 28 days before enrollment;

            6) The imaging findings showed that the tumor formed deep ulcer, or had invaded important blood vessels, or the researchers judged that fatal massive hemorrhage might occur during the follow-up study;

            7) Regardless of the severity, there are any signs or history of bleeding constitution; In the first 4 weeks, there was any bleeding or bleeding event ≥ CTC AE 3; There are unhealed wounds, ulcers or fractures;

            8) In the first 6 months of the study, patients with arteriovenous thrombotic events such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism occurred;

            9) Patients with history of aneurysm / dissection;

            10) Patients with history of epilepsy or ataxia of nervous system need treatment;

            11) Those who have a history of psychotropic drug abuse and can't quit or have mental disorder;

            12) Patients with history of peripheral nervous system diseases and muscle strength below grade 3;

            13) Those who had participated in other anti-tumor drug clinical trials or were conducting other clinical trials within 4 weeks before enrollment;

            14) They can not tolerate the drugs used in this project, including treprizumab, albumin, paclitaxel and cisplatin, or have a history of severe hypersensitivity to any component;

            15) According to the judgment of the researchers, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the trial.