Recurrent Respiratory Papillomatosis
Conditions
Interventions
Experimental group A:Bevacizumab
Experimental group B: Bevacizumab
Experimental group C:sintilimab
Experimental group D:Bevacizumab+sintilimab
Sponsors
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with recurrent respiratory papilloma confirmed by histology. 2. The age of cohort A is less than 18 years old; The age of cohort B, C and D is = 18 years; 3. Patients who have received = 4 operations for recurrent respiratory papilloma within 1 year; Or patients with lesions involving larynx, trachea, bronchus and or lung tissue; Or patients with Derkay score = 20. 4. ECOG 0-1 points; Life expectancy>3 months; 5. The function of main organs is normal, that is, they meet the following standards: 1) Hemoglobin (Hb) = 95g/L; 2) Neutrophil (ANC) = 1.5 × 109/L 3) Platelet count (PLT) = 80 × 109/L 4) Serum creatinine (Cr) = 1.5 × Upper limit of normal (ULN), blood urea nitrogen (BUN) = 2.5 × Upper limit of normal (ULN); 5) Total bilirubin (TB) = 1.5ULN; AST and ALT = 2.5 × ULN 6) Albumin (ALB) = 35 g/L; 7) Prothrombin time (PT) and partial prothrombin time (PTT) = 1.2 × ULN 8) Left ventricular ejection fraction = 50%; 9) The blood pressure was controlled within 140/90 mmHg before enrollment. 6. Women of childbearing age must have taken reliable contraceptive measures or conducted pregnancy test (serum or urine) within 7 days before enrollment, and the result is negative, and are willing to use appropriate methods of contraception during the test and 8 weeks after the last administration of the test drug. For males, it is necessary to agree to use appropriate methods of contraception or surgical sterilization during the test and within 8 weeks after the last administration of the test drug; 7. Sign the informed consent form (or signed by the legal representative) to prove that they understand the purpose of the study and the operation required by the study, and are willing to participate in the study
Exclusion criteria
Exclusion criteria: 1.Patients will not be admitted to Group A, Group B and Group D if they meet any of the following conditions: Patients who have accepted any angiogenisis inhibitors, such as sunitinib, sorafenib, imatinib, famitinib, apatinib, regafenib etc; Daily hemoptysis of 2.5ml or more during 2 months before enrollment; 2.Patients will not be admitted to Group C and Group D if they meet any of the following conditions: 1) He has received antibody treatment such as PD-1, PD-L1 and CTLA-4 in the early stage; 2) Subjects have any active autoimmune disease or history of autoimmune disease; 3) Cortisol (greater than 10 mg/day prednisone or equivalent dose) or other systemic immunosuppressive drugs (except inhaled or topical corticosteroids) or prednisone or equivalent of alternative therapy with a dose greater than 10 mg/day are required within 14 days before the study treatment; 4) Patients with objective evidence of interstitial lung disease in the past and at present; 5) Live vaccine should be inoculated less than 4 weeks before the study medication or possibly during the study period; 3.Patients have ever received systemic treatment for recurrent respiratory papilloma in recent 3 months: such as HPV vaccine, interferon, cidofovir, celecoxib, etc; 4.Abnormal coagulation function (INR> 1.5 or PT>1.2ULN or PTT> 1.2ULN), Patients with bleeding tendency or are undergoing thrombolysis or anticoagulation; treated with anticoagulant or vitamin K antagonists such as warfarin, heparin or their similar drugs; 5.Urinary protein=++, unless 24 hours urinary protein quantitative < 1.0 g; 6.Patients with any disease that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation: such as active gastrointestinal ulcers, known metastases in the lumen, inflammatory bowel disease, history of abdominal fistula, abdominal perforation or intra-abdominal abscess within 28 days before enrollment; 7.Patient with malignant tumors. The cured cervical carcinoma in situ, nonmelanoma skin cancer and superficial bladder tumors are permitted [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor-infiltrating basement membrane)]. 8.Unrelieved toxic reactions higher than NCI CTC AE (5.0) grade 1 due to any previous treatment 9.Allergic to any tested drug ingredient; 10.Patients with uncontrolled diseases include, but are not limited to: hypertension, bleeding, infection, liver and kidney disease, diabetes, cardiovascular diseases, lung diseases, unhealed wounds, and severe chronic gastrointestinal diseases with diarrhea, psychiatric or social problems that may limit compliance with study , significantly increase the risk of AE, or affect the subject's ability to provide written informed consent; 11.Patients with any of the following cardiovascular diseases in the past six months: cerebral vascular accident (CVA) or transient cerebral ischemia (TIA), arrhythmia (including QTc interval :=450 ms in men , =470 ms in women), angina, coronary artery angioplasty, or cardiac stent, pulmonary embolism, Patients with deep vein thrombosis untreated or less than 6 weeks of anticoagulation, arterial thrombosis, grade III or IV heart failure defined by the New York Heart Association (NYHA) functional grading system, pericardial disease with < 50% of left ventricular ejection fraction (LVEF) suggested by heart color ultrasound examination, Or the electrocardiogram suggests acute ischemia or active conduction system abnormalities; 12.Patients wi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Group A:Frequency of debulking surgery during the 12 months pre and 12 months post treatment;Group B,C,D:Objective Response; | — |
Secondary
| Measure | Time frame |
|---|---|
| Group A:Objective Response;Group B,C,D:Frequency of debulking surgery during the 12 months pre and 12 months post treatment;Derkay severity score pre and post treatment;Voice Handicap Index-10 pre and post treatment;adverse effect; | — |
Countries
China
Contacts
Public ContactZhu Dongyuan
Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences
Outcome results
None listed