urothelial carcinoma
Conditions
Interventions
Combination Therapy Group:Sintilimab Combined with Vorolanib
Sponsors
Third Medical Center, Chinese PLA General Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 85 Years
Inclusion criteria
Inclusion criteria: 1.Signed written informed consent obtained prior to implementation of any trial-related procedures. 2.Male or female patients aged =18 and =85 years. 3.Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-2. 4.Histopathologically confirmed unresectable locally advanced or metastatic urothelial carcinoma (including tumors originating from renal pelvis, ureter, or urethra; tumors with mixed histology are permitted if urothelial carcinoma component >50%). 5.HER2-negative status AND either:Unsuitable for or refusing cisplatin-based first-line systemic therapy, OR Progressive disease after systemic therapy(Note: Patients who recurred >12 months after completing neoadjuvant/adjuvant chemotherapy are eligible). 6.At least one measurable lesion per RECIST 1.1 criteria (lesion not previously irradiated). Remark: Previously irradiated lesions may be considered measurable if documented progression exists at enrollment. 7.Life expectancy =3 months. 8.Adequate organ function (within 14 days prior to enrollment), defined as: 9.Hematological (without transfusion/G-CSF support within 14 days): i. Hemoglobin (HB) =90 g/L ii. Absolute neutrophil count (ANC) =1.5 × 10?/L iii. Platelets (PLT) =100 × 10?/L Biochemical: iv. Total bilirubin (T-BIL) =1.5 × ULN v. ALT/AST =2.5 × ULN (=5 × ULN if liver metastases present) vi. Serum creatinine =2 × ULN OR creatinine clearance >20 mL/min (Cockcroft-Gault formula) vii. INR/aPTT =1.5 × ULN (for non-anticoagulated patients; anticoagulated patients must maintain therapeutic range). 9.No systemic corticosteroid therapy within 4 weeks prior to treatment (physiologic replacement doses allowed). 10.Fertile male/female patients [premenopausal women without hysterectomy/bilateral oophorectomy/salpingectomy, or menopausal<1 year since last menstruation)] must use highly effective contraception (e.g., oral contraceptives, IUD, sexual abstinence, or barrier methods with spermicide) during treatment and for 12 months post-treatment.
Exclusion criteria
Exclusion criteria: 11)Urine routine suggestive of urinary protein =++ and confirmed 24-hour urine protein quantification >1.0g; 12)Patients with mental disorders and unable to cooperate with the treatment; 15. History or evidence of disease that may interfere with the test results, prevent the subject from participating in the entire study, abnormal values of treatment or laboratory tests, or other conditions that the investigator believes are not suitable for enrolment The investigator believes that there are other potential risks unsuitable for participation in this study.1. malignant disease other than uroepithelial bladder cancer diagnosed within 5 years prior to the first dose (excluding radically treated basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ that has undergone radical resection); 2. currently being treated in an interventional clinical study or have been treated with another investigational drug or with an investigational device within 4 weeks prior to the first dose; 3. prior therapy with: anti-PD-1, anti-PD-L1, or anti-PD-L2 agents or agents targeting another stimulatory or synergistic inhibitor of T-cell receptors (e.g., CTLA-4, OX-40, CD137); 4. systemic systemic therapy with proprietary Chinese medicines with anti-tumour indications or drugs with immunomodulatory effects (including thymidine, interferon, interleukin, except for topical use for the control of hydrothorax) within 2 weeks prior to the first dose; 5. Active autoimmune disease requiring systemic therapy (e.g., use of disease-mitigating medications, glucocorticoids, or immunosuppressive agents) has occurred within 2 years prior to the first dose. Alternative therapies (e.g., thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic therapy; 6. is receiving systemic glucocorticoid therapy (excluding topical glucocorticosteroids by nasal spray, inhalation or other routes) or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study; Note: Physiological doses of glucocorticoids (=10 mg/day of prednisone or equivalent) are permitted; 7. known allogeneic organ transplantation (except corneal transplantation) or allogeneic haematopoietic stem cell transplantation; 8. known hypersensitivity to the active ingredient or excipient of the study drug sindilizumab as well as combination chemotherapy drugs;; 9. have not fully recovered from any intervention-induced toxicity and/or complications (i.e., = Grade 1 or at baseline, excluding malaise or alopecia) prior to initiation of treatment; 10. known history of human immunodeficiency virus (HIV) infection (i.e., HIV1/2 antibody positive); 11. Untreated active hepatitis B (defined as HBsAg positivity accompanied by a detectable HBV-DNA copy number greater than the upper limit of normal in the laboratory section of the research centre); Note: Subjects with hepatitis B meeting the following criteria may also be enrolled: 1) HBV viral load <1000 copies/ml (200 IU/ml) prior to the first dose, and subjects should receive anti-HBV therapy to avoid viral reactivation for the entire duration of the study chemotherapeutic drug therapy 2) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring of viral reactivation is needed 3) Subjects with active HCV infection (HCV antibody positive and HCV-RNA leve
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS;Disease Control Rate, DCR;Overall Survival, OS;Adverse Event, AE; | — |
Countries
China
Contacts
Public ContactGu Liangyou
Third Medical Center, Chinese PLA General Hospital
Outcome results
None listed