Thyroid cancer bone metastasis
Conditions
Interventions
experimental group:PD-1 monoclonal antibody combined with zoledronic acid and denosumab
control group:PD-1 monoclonal antibody combined with zoledronic acid
Sponsors
Affiliated Sixth People's Hospital, Shanghai Jiaotong University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged >= 18 years, regardless of gender. 2. Locally advanced or metastatic thyroid cancer. 1) Locally advanced refers to T4AnyN M0 in TNM staging; 2) Metastatic refers to AnyT AnyN M1 in TNM staging. 3. Differentiated thyroid cancer confirmed by histology or cytology: papillary, follicular and Hurthle cells, or poorly differentiated cancer. 4. Disease progression occurred within 14 months before randomization. 1) Disease progression refers to the disease progression confirmed by RECIST V1.1. 2) Disease progression was within 14 months before randomization (= 10mm, or lymph node lesions with the short diameter >= 15mm. 2) The lesions after previous external radiotherapy or ablation treatment can also be used as measurable target lesions if they have clearly progressed according to RECIST V1.1 and the longest diameter is >= 10mm. 3) Bone metastatic lesions (including identifiable soft tissue components) are not regarded as measurable lesions. 6. RAI refractory: After nail ablation, in the absence of interference from exogenous iodine load, thyroid stimulating hormone (TSH) (>30mU/L) stimulation can be diagnosed as iodine refractory if any of the following occurs Thyroid cancer: 1) At least one measurable lesion showed no iodine intake during 131I treatment or scanning. 2) Although the measurable lesions have iodine uptake, at least one measurable lesion progressed within 14 months after the last 131I treatment (dose of 3.7-7.4GBq or 100-200mCi) (evaluated by RECIST V1.1). 3) The cumulative 131I dose of radioactive iodine treatment is >= 22GBq or 600mCi. 7. Not suitable for therapeutic surgery or radiotherapy. 8. Patients with a history of brain metastases must meet: have completed whole brain radiotherapy, stereotactic radiosurgery or surgical complete resection, and have received stable dose glucocorticoid therapy for at least 2 weeks before randomization (the maximum dose is 16 mg per day Dexamethasone or equivalent dose), and can maintain a stable dose after randomization, without symptoms of brain metastasis or subdural metastasis. 9. TSH inhibition therapy is well tolerated, and TSH= 9.0g/dl; 2) Absolute neutrophil count (ANC) >= 1,500/mm3; 3) Platelet (PLT) count >= 100,000/mm3; 4) The total bilirubin (TBIL) level is less than 1.5 times the upper limit of normal (ULN); 5) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 50ml/min. Note: Ccr=(140-age) x body weight (kg)/[72 x Scr(mg/dl)] or Ccr=[(140-age) x weight(kg)]/[0.818 x Scr(umol/L)] Women calculated by the result x 0.85 11. The ECOG PS score is 0-2 points. 12. The expected survival period is >= 12 weeks. 13. Female patients must meet: 1) Menopause (defined as no menstruation for at least 1 year), or 2)
Exclusion criteria
Exclusion criteria: 1. Received tyrosine kinase inhibitors, monoclonal antibodies targeting vascular endothelial growth factor or vascular endothelial growth factor receptors or other targeted drugs within 4 weeks before randomization. 2. Have received any chemotherapy (except low-dose chemotherapy for the purpose of radiation sensitization), radiotherapy and other anti-cancer treatments within 4 weeks before randomization. 3. A history of tooth extraction and osteonecrosis of the jaw within 28 days. 4. In the 5 years before randomization, there have been cancers whose primary site or histological type is different from thyroid cancer, or cancers coexisting with thyroid cancer but whose primary site or histological type is different, but cervical carcinoma in situ, has been treated Except for basal cell carcinoma and superficial bladder tumors (non-invasive tumors, carcinoma in situ and tumors invading the propria propria). 5. Major surgery, open tissue biopsy, or severe trauma occurred within 4 weeks before randomization. 6. There is an unhealed wound, ulcer or fracture. 7. Evidence or medical history of bleeding constitution or coagulopathy. 8. Are using antiplatelet drugs (except for low-dose aspirin with daily dose = Grade 3 [General Term Standards for Adverse Events Version 4.0 (CTCAE V4.03)] occurred within 3 months before randomization. 11. Clinically significant heart disease occurred within 6 months before randomization, including congestive heart failure with severity greater than New York Heart Association grade II, unstable angina (angina pectoris at rest), new angina pectoris (random 3 months before treatment) or myocardial infarction. 12. Ventricular arrhythmia that requires antiarrhythmic treatment; QTc > 480ms; hypertension that cannot be well controlled after 2 or more antihypertensive drugs (systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg). 13. Thrombotic or embolic venous or arterial events occurred within 6 months before randomization, such as cerebrovascular accidents, including transient ischemic attack, arterial thrombosis, deep vein thrombosis and pulmonary embolism. 14. Infections with severity> Grade 2 (CTCAE V4.03). 15. Any toxicity (including neurotoxicity, except hair loss) of severity > 2 (CTCAE V4.03) caused by any previous treatment has not been eliminated. 16. Human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection active period, hepatitis B virus (HBV) infection active period (HBV-DNA > 1000 copies/ml, except for HBV carriers). 17. Seizures that require medication (such as steroids or anti-epileptic drugs). 18. Use strong CYP3A4 inducers (such as phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital, etc.) within 7 days before randomization. 19. Use biological response modifiers (such as granulocyte colony stimulating factor, etc.) within 21 days before randomization. 20. Drug abuse, medical, psychological or social diseases that may interfere with participating in research or the evaluation of research results. 21. Any malabsorption disease. 22. Any disease that is unstable or may endanger patient safety and research compliance. 23. During the trial period or within 4 weeks before randomization, receive treatment from other clinical studi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS;Adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR;Duration of Response, DoR;Disease Control Rate, DCR; | — |
Countries
China
Contacts
Public ContactHu Haiyan
Affiliated Sixth People's Hospital, Shanghai Jiaotong University
Outcome results
None listed