cisplatin intolerant cT2-T4aN0M0 bladder urothelial carcinoma
Conditions
Interventions
Experimental group:Dose escalation plan: During the dose escalation phase, Palbociclib is administered at an initial dose of 100mg qd, and two dose groups, 100mg qd and 125mg qd, are designed. Take a
Experimental group:Phase II of the second phase of the study: An extended study was conducted to explore the effectiveness and safety of the combination regimen of Palbociclib and Tislelizumab Injecti
Sponsors
Sun Yat-sen Memorial Hospital,Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: ? Voluntarily participate in this experiment, be able to provide a written version of the informed consent form, and understand and agree to comply with the requirements and evaluation schedule of this study. ? The age at the date of signing the informed consent form is 18 years old or above. ? There are residual lesions after TURBT operation. Based on the TNM staging of bladder cancer of AJCC 8th Edition, patients with cT2 T4aN0M0 bladder urothelial carcinoma were confirmed histologically and evaluated imageologically; Patients with mixed type tumors in histology are required to have urothelial carcinoma as the dominant factor (at least 50%). ? Genomic testing has found patients with cell cycle related gene activation type mutations or CNV changes that activate cell cycle related pathways, including but not limited to CNV deletions in CDKN2A and CDKN2B, E2F3 CNV amplification, etc. ? ECOG physical fitness status 0 or 1 (Appendix 1). ? Patients who are intolerant to cisplatin drug therapy or do not accept cisplatin drug therapy, and those who are intolerant to cisplatin chemotherapy, must meet at least one of the following criteria: ECOG physical fitness status>1 or Karnofsky physical fitness status between 60% and 70%; The creatinine clearance rate is below 60ml/min (Appendix 7); According to the National Cancer Institute's Common Terminology for Adverse Events (NCI-CTCCAE) 5th edition, hearing loss = level 2; Peripheral neuropathy = level 2 in NCI-CTCAE 5th edition; Suffering from New York Heart Association grade III or above heart failure (Appendix 2). ? After evaluation by the researchers, it is necessary to undergo radical cystectomy after neoadjuvant therapy and meet the surgical indications for radical cystectomy, and they are willing to accept the surgery. ? TURBT tumor tissue samples must be provided, and relevant pathological reports must be provided. Fresh surgical tissue or pathological white slides can be selected for examination. ? The patient's organ function is good, as measured by the laboratory test values during the screening period (obtained = 14 days before enrollment): a. When screening the following items, patients are not allowed to use growth factor support for = 14 days before sample collection: i. Neutrophil absolute count = 1.5x109/L ii. Platelets = 90 × 109/L iii. Hemoglobin = 90g/L b. International standardized ratio or activated partial thromboplastin time = 1.5 upper limit of normal value (ULN) c. Serum total bilirubin = 1.5 x ULN (if Gilbert syndrome or indirect bilirubin concentration shows an increase in liver extraneous factors, it should be = 3 x ULN) d. AST, ALT, and alkaline phosphatase = 2.5 x ULN e. Pulmonary function suggests tolerability for major abdominal surgery ? Women who are not pregnant or have fertility must be willing to take efficient contraceptive measures during the study period, and within = 120 days after the last dose of tirizumab or chemotherapy (whichever occurs later), and must have a negative urine or serum pregnancy test result within = 7 days before enrollment. Unsterilized males must be willing to take efficient contraceptive measures during the study period and within = 120 days after the last dose of tirizumab or chemotherapy (whichever occurs later).
Exclusion criteria
Exclusion criteria: ? Previously received therapy targeting PD-1, PD-L1, PD-L2, CTLA4, or other antibodies or drugs specifically targeting T cell co stimulation or checkpoint channels. ? Within 28 days prior to enrollment, receive other approved systemic anti-cancer treatments or systemic immune modulators (including but not limited to interferon, interleukin-2, and tumor necrosis factor). ? He has received radiotherapy for bladder cancer in the past. ? Previously received drug treatment for tumors, except for the following: a For patients who have previously received systemic chemotherapy, there should be a no treatment interval of at least 12 months from the last treatment to the start of neoadjuvant therapy; b. Local intravesical chemotherapy or immunotherapy should be completed at least one week before the start of the study of neoadjuvant therapy ? Within 28 days prior to enrollment, major surgery or major trauma occurred (implantation of vascular access devices and TURBT are not considered major surgeries). ? Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral treatment within 14 days prior to enrollment (HBV infection shall be treated according to exclusion criteria 11). ? Received a live vaccine within 28 days prior to enrollment (seasonal influenza vaccines are usually inactivated vaccines and therefore allowed to be used. Intranasal vaccines are considered live vaccines and therefore not allowed to be used). ? Active autoimmune diseases that require systemic treatment are evaluated by researchers as having an impact on the research treatment. ? Long term and extensive use of hormones or other immunosuppressive agents are required, which researchers have assessed as having an impact on the study and treatment. ? The investigator identified the history of potassium, sodium, calcium abnormalities or hypoalbuminemia, interstitial lung disease, noninfectious pneumonia or other uncontrolled systemic diseases that may affect the treatment, including diabetes, hypertension, cardiovascular diseases (if there were active heart diseases within 6 months before enrollment, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure and ventricular arrhythmia requiring drug treatment), etc. ? Untreated chronic hepatitis B subjects or carriers of hepatitis B virus (HBV) with HBV DNA = 500 IU/mL (2500 copies/mL) are not allowed to enter the study. Note: Patients with inactive hepatitis B surface antigen carriers or stable active HBV infection (HBV DNA<500 IU/mL [2500 copies/mL]) after continuous antiviral treatment can be enrolled. HBV DNA testing is only performed in patients with positive antibodies against hepatitis B core antigen. ? Patients with active hepatitis C are not eligible for enrollment. Patients who tested negative for HCV antibodies during the screening period, or those who tested positive for HCV antibodies and tested negative for HCV RNA, can be enrolled. Only patients who test positive for HCV antibodies need to undergo HCV RNA testing. ? Have a history of immunodeficiency (including positive human immunodeficiency virus HIV testing, other acquired or congenital immunodeficiency diseases) or a history of allogeneic stem cell transplantation or organ transplantation (Appendix 3). ? Known to be allergic to other monoclonal antibodies. ? Known to be allergic to any investigational drug or excipient. ? Patients who have not recovered to baseline or stable l
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity; | — |
Secondary
| Measure | Time frame |
|---|---|
| pathological complete remission rate; | — |
Countries
China
Contacts
Public ContactLin Tianxin
Sun Yat-sen Memorial Hospital,Sun Yat-sen University
Outcome results
None listed