Bladder Cancer
Conditions
Interventions
Experimental group:Vedicitumab neoadjuvant and adjuvant full-course treatment combined with BCG bladder instillation
Sponsors
Sun Yat-sen Memorial Hospital of Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in this trial, able to provide a written informed consent form, and can understand and agree to comply with the requirements and assessment schedule of this study. 2. Male or female aged 18 years or older on the day of signing the informed consent form. 3. Histologically confirmed urothelial carcinoma of the bladder, staged as Ta, T1, or with carcinoma in situ (CIS). For patients with mixed-type tumors, the urothelial carcinoma component must be predominant (>=70%). 4. According to the EAU NMIBC prognostic risk stratification standards (based on WHO 2004/2016 or 1973 grading system), patients must precisely meet the definition of 'High Risk' or 'Very High Risk.' The specific criteria are as follows (meeting any one is sufficient): First, define clinical risk factors as the following four items: (1) Multiple tumors (number > 2) (2) Tumor diameter > 3 cm (3) Tumor recurrence (4) Age > 70 years Patients meeting any of the following combinations of stage, grade, and risk factors can be included: (1) Presence of high-risk pathological features: 1) Any T1, high-grade/G3 tumor (T1 HG/G3). 2) Urethral prostatic involvement with carcinoma in situ. 3) Presence of variant subtypes of urothelial carcinoma. 4) Presence of lymphovascular invasion (LVI). (2) Presence of carcinoma in situ (CIS) (excluding the situations mentioned in point a above). (3) No CIS, but the combination of stage, grade, and risk factors meets any of the following conditions: 1) T1, G2 tumor (T1 G2), with at least one clinical risk factor. 2) Ta, high-grade/G3 or T1, low-grade tumor (Ta HG/G3 or T1 LG), with at least two clinical risk factors. 3) Ta, low-grade/G2 or T1, G1 tumor (Ta LG/G2 or T1 G1), with all three clinical risk factors. 5. Before starting neoadjuvant therapy, provide tumor tissue specimens obtained through diagnostic biopsy or transurethral resection. The specimens must be tested at a central laboratory or a qualified local laboratory and confirmed as HER2 overexpression (defined as immunohistochemistry IHC score of 2 or 3). 6. Before neoadjuvant therapy, imaging must allow for lesion assessment, or urine FISH/cytology positive/DNA methylation positive. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. The patient's organ function is adequate, as measured by the following screening laboratory test values (obtained =1.5×10^9/L 2) Platelets >=90×10^9/L 3) Hemoglobin >=90 g/L (2) International normalized ratio or activated partial thromboplastin time =1.5 times the upper limit of normal (ULN) (3) Serum total bilirubin <=1.5×ULN (if Gilbert's syndrome or indirect bilirubin elevation is of extrinsic hepatic origin, it should be <=3×ULN) (4) AST, ALT, and alkaline phosphatase <=2.5×ULN (5) Pulmonary function indicating the patient can tolerate surgery 9. Women who are not pregnant or of childbearing potential must be willing to use effective contraception during the study and for =180 days after the last dose of vidacizumab, and must have a negative urine or serum pregnancy test within <=7 days before enrollment. Men who have not undergone sterilization must be willing to use effective contraception during the study and for =180 days after the last dose of vidacizumab.
Exclusion criteria
Exclusion criteria: 1. According to the EAU risk stratification, patients who meet the definition of "Low Risk" or "Intermediate Risk". (1) "Low Risk" is defined as: 1) Primary, single, TaT1 LG/G1 tumor, diameter <3 cm, no CIS, and patient age =70 years. 2) Primary Ta LG/G1 tumor, no CIS, and at most only 1 additional clinical risk factor. (2) "Intermediate Risk" is defined as: 1) Any patient without CIS who does not meet the criteria for "Low Risk," "High Risk," or "Very High Risk." 2. Diagnosed or suspected muscle-invasive (=T2), lymph node metastasis (N), or distant metastasis (M1) of bladder cancer. 3. Previously received therapies targeting PD-1, PD-L1, PD-L2, CTLA4, LAG-3, HER2, Nectin-4, or other antibodies or drugs specifically targeting T-cell co-stimulation or checkpoint pathways. 4. Received other approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor) within 28 days before enrollment. 5. Previously received radiotherapy for bladder cancer. 6. Previously received drug treatment for tumors, except for the following: (1) For patients who have previously undergone systemic chemotherapy, a treatment-free period of at least 12 months from the last treatment to the start of neoadjuvant drug therapy; (2) Local intravesical chemotherapy or immunotherapy completed at least 2 weeks before the start of the study neoadjuvant drug therapy. 7. Underwent major surgery or experienced major trauma within 28 days before enrollment (implantation of vascular access devices and TURBT are not considered major surgery). 8. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days before enrollment (HBV infection is handled according to Exclusion Criterion 11). 9. Received a live vaccine within 28 days before enrollment (seasonal injected influenza vaccines are usually inactivated and therefore allowed; intranasal vaccines are live vaccines and not allowed). 10. Active autoimmune disease requiring systemic treatment that, in the investigator's assessment, may affect the study treatment. 11. Requires long-term use of high-dose hormones or other immunosuppressants, which the investigator deems may affect the study treatment. 12. Investigator-identified abnormalities in potassium, sodium, calcium, hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases that may affect treatment, including diabetes, hypertension, cardiovascular diseases (such as active heart disease within 6 months prior to enrollment, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and ventricular arrhythmias requiring medication), etc. 13. Subjects with untreated chronic hepatitis B with HBV DNA =500 IU/mL (2500 copies/mL) or hepatitis B virus carriers are not allowed to enter the study. Note: Inactive hepatitis B surface antigen carriers or patients with active HBV infection stabilized after continuous antiviral treatment (HBV DNA <500 IU/mL) may be enrolled. HBV DNA testing is only performed in patients who are positive for antibodies against hepatitis B core antigen. 14. Patients with active hepatitis C are not eligible for enrollment. Patients who test negative for HCV antibodies during the screening period, or those who test positive for HCV antibodies but HCV RNA negative, may be enrolled. Only patients positive
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Overal Survival;Metastasis-Free Survival;Quality of Life;Bladder-Intact Disease-Free Survival;2-year Disease-Free Survival;Health economics evaluation;Safety indicators;Clinical completed rate; | — |
Primary
| Measure | Time frame |
|---|---|
| 2-year Event-Free Survival; | — |
Countries
China
Contacts
Public ContactWang He
Sun Yat-sen Memorial Hospital of Sun Yat-sen University
Outcome results
None listed