Bladder cancer
Conditions
Interventions
Case series (Stage 1):SHR-1210 combined with cisplatin/gemcitabine
experimental arm (Stage 2):SHR-1210 combined with cisplatin/gemcitabine
control arm (Stage 2):cisplatin+gemcitabine
Sponsors
Cancer Hospital of Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be enrolled in this study: 1. Aged >=18 years old; 2. Expected survival >=3 months; 3. The physical state score of the eastern cancer cooperation group (ECoG) must be 0-1; 4. At least one measurable lesion meeting recistv1.1 standard before diagnostic electrosurgical resection (according to recistv1.1, the long diameter of spiral CT scanning of the measurable lesion >=10mm or the short diameter of enlarged lymph nodes >=15mm); 5. Histopathologically confirmed locally advanced bladder urothelial carcinoma without evidence of metastasis. Mixed carcinoma requires that the main histological type is urothelial carcinoma subtype; 6. Chemotherapy without platinum containing regimen in the past; 7. clinically diagnosed as locally advanced bladder cancer, it can be associated with or without pelvic lymph node enlargement (cT2-T4a, N0-1, M0); 8. Suitable and planned radical cystectomy (according to the guidelines); 9. Adequate hematology and end organ function within 4 weeks before the first study treatment, as defined below: It has sufficient bone marrow reserve and organ function 1) Neutrophil count (ANC) >=1500 / mm3 (no granulocyte colony stimulating factor support in the first 2 weeks of randomization); 2) White blood cell count (WBC) > 2500/uL; 3) Lymphocyte count >=500/uL; 4) Platelet count (PLT) >=100000/mm3 (no blood transfusion in the first cycle and 2 weeks before randomization); 5) Hemoglobin (HB) >=9 g/dl (patients can receive blood transfusion or erythropoiesis treatment to meet this standard); 6) Serum creatinine (CR) =60ml / min (Cockcroft Gault formula); 7) Total bilirubin (bil) <=1.5 ULN; 8) Aspartate aminotransferase (AST / SGOT) or alanine aminotransferase (ALT / SGPT) level <=2.5 ULN (known patients with Gilbert disease, their serum bilirubin level <=3 ULN (available); 9) International normalized ratio (INR) <=1.5, prothrombin time (PT) and activated partial thromboplastin time (APTT) <=1.5 ULN (this is only applicable to patients who have not received therapeutic anticoagulant therapy; Patients receiving therapeutic anticoagulation should take a stable dose); 10. Fertile women: they must agree to abstinence (avoid heterosexual intercourse) or use reliable and effective contraceptive methods from the signing of informed consent to at least 120 days after the last administration of the study drug. And the serum hCG test must be negative within 7 days before starting the study treatment; And must be non lactation. If a female patient has menstruation, has not yet reached the postmenopausal state (continuous non menstruation time = 12 months, no other reason is found except menopause), and has not received sterilization surgery (such as hysterectomy, bilateral tubal ligation or bilateral oophorectomy), the patient is considered to be fertile. 11. Male patients whose partners are women of childbearing age must agree to abstinence or use reliable and effective contraceptive methods from the signing of informed consent to at least 120 days after the last administration of the study drug. Male subjects must also agree not to donate sperm during the same period of time. Male subjects whose partners are pregnant must use condoms and do not need to use other contraceptive methods; 12. The subjects are willing, understand and sign the informed consent form, and can abide by the agreement.
Exclusion criteria
Exclusion criteria: 1. With any active autoimmune disease or history of autoimmune disease; 2. Any systemic steroid therapy or immunosuppressive therapy within two weeks prior to the first dose of trial treatment; 3. With severe allergic reaction to monoclonal antibodies; 4. Any untreated central nervous system (CNS) metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least one month prior to registration for protocol therapy and without any clinical neurologic symptoms), and have not received steroids therapy for at least two weeks; 5. Patients with hypertension or uncontrolled blood pressure on medication; 6. With uncontrolled heart disease or any heart clinical symptom; 7. Abnormal coagulation(INR>2.0PT>16s). Low-dose aspirin and low-molecular-weight heparin are allowed for prophylactic use for patients with bleeding tendency or for patients who are receiving thrombolysis or anticoagulation treatments; 8. Any bleeding event with grade 2 or above as defined per CTCAE 5.0 within 4 weeks before the first administration; 9. Imaging shows that important blood vessels have been invaded or have the danger to be invaded and could cause fatal bleeding during the trail treatment; 10. Arteriovenous thrombosis within 6 months before the first administration; 11. Less than 4 weeks after completion of previous chemotherapy (including platinum chemotherapy) and surgery prior to the first dose of trial treatment ; less than 2 weeks after palliative radiotherapy; less than 5 drug half-lives after the first administration for previous molecular targeted treatment; or adverse events (except hair loss) caused by the previous treatment did not recover to <=CTCAE Grade 1; 12. Radiation enteritis caused by pelvic radiotherapy within 12 months prior to the first dose of trial treatment; 13. With active infection; 14. Known interstitial pneumonia or non-infectious pneumonia treated with corticosteroids, or suspected drug-related pulmonary toxicity which could interfere with the evaluation of safety of the study drugs; 15. With immune deficiency diseases, including HIV infection or other acquired and congenital immune deficiency diseases, or known active tuberculosis; 16. Known active hepatitis B or hepatitis C; 17. Patients also had other malignant cancers at the same time or in the past 5 years; 18. Previously received PD-1 antibody, PD-L1 antibody, CTLA-4 antibody or any other antibody acting on T cell co-stimulation or immune checkpoint pathways; 19. Patients have received any live vaccine within 4 weeks prior to the first dose of trial treatment; 20. Patients who refuse to receive or are not tolerable for cisplatin-based neoadjuvant chemotherapy; 21. In the judgment of the investigator, patients may have other factors that may affect the results of the trail or cause the trail to be forced to terminate midway; 22. Pregnant or breastfeeding patients; 23. Patients are unsuitable for the trail treatment or unwilling or unable to comply with the protocol according to judgment of the researchers.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| pCR; | — |
Secondary
| Measure | Time frame |
|---|---|
| AE;DFS;OS;12-month OS%;QoL; | — |
Countries
China
Contacts
Public ContactNianzeng Xing
Cancer Hospital of Chinese Academy of Medical Sciences
Outcome results
None listed