Upper tract urothelial carcinoma
Conditions
Interventions
experimental group:Neoadjuvant therapy with toripalimab + gemcitabine + cisplatin
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Over 18 years old, under 75 years old, histologically or cytologically confirmed UTUC, clinical stage cT3-4N0-2M0, or cT1-2N0M0 but combined with any of the following high-risk factors: • Hydronephrosis •Tumor meridians > 2 cm •Urinary exfoliative cytology shows high-grade tumors •Ureteroscopic biopsy reveals high-grade tumors •Multifocal tumors •Patients who have undergone radical cystectomy for bladder cancer •Variant histology Most of the patients with the above clinical stages have locally progressive UTUC and have not yet had obvious distant metastases visible on imaging, but the local invasion of the tumor is severe, may invade extra-organ tissues or adjacent organs, and there is a high risk of micrometastasis, so these patients are most likely to benefit from neoadjuvant therapy 2. Urologists participating in clinical trials assessed to be able to perform radical nephroperectomy 3. Baseline examination: neutrophil > 1500 cells/mm^3, platelet > = 100,000 cells/mm^3, bilirubin =60ml/min. 4. Agree to provide tissue examination specimens 5. Normal function of major organs (14 days before enrollment), that is, meet the relevant laboratory examination criteria for chemotherapy and immunotherapy 6. Have not received systemic corticosteroid medication within 4 weeks prior to treatment 7. Men of reproductive potential or females with the possibility of becoming pregnant, must use a highly effective method of contraception (such as oral contraceptives, intrauterine devices, sexual desire control or barrier contraception in combination with spermicide) during the course of the trial and continue contraception for 12 months after the end of treatment. If the participant is a woman of childbearing age, serum blood tests are done to confirm that she is not pregnant 8. Subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with follow-up
Exclusion criteria
Exclusion criteria: 1.Patients with concomitant non-organ localized bladder cancer 2.Systematic anti-tumor therapy (including chemotherapy, immunotherapy, etc.) for UTUC and radiotherapy with the tumor area as the target area. Patients who had undergone transurethral resection of bladder tumor for diagnose and/or local cystectomy and those who had undergone intravesical instillation chemotherapy only were allowed to enroll 3.Known or suspected hypersensitivity to toripalimab, gemcitabine and cisplatin 4.Patients with existing or combined bleeding disorders 5.Other uncontrolled inoperable patients 6.Patients with positive HIV test results 7.Patients with active HBV or HCV; HBsAg or HBcAb positive, and HBV DNA copy number >= 1000 IU/ml detected at the same time; HCV antibody positive patients can only be enrolled in this study when HCV RNA PCR test results are negative. 8.Patients with a clear history of active tuberculosis; 9.Active autoimmune disease requiring systemic treatment (such as the use of corticosteroids or immunosuppressive drugs) within the past 2 years, but related replacement therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for renal or pituitary insufficiency) are allowed; 10.Other serious, uncontrolled concomitant diseases that may affect protocol compliance or interfere with interpretation of results, including active infection, uncontrolled diabetes, cardiovascular disease (Grade III or IV heart failure defined by New York Heart Association classification, Grade II or higher heart block, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina pectoris, cerebral infarction within 3 months, etc.) or pulmonary disease (history of interstitial pneumonia, obstructive pulmonary disease, and symptomatic bronchospasm); 11.Patients who have received live vaccinations within 4 weeks before the start of treatment; 12.Patients who have previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation; 13.Patients who have undergone major surgical procedures (excluding diagnostic surgical procedures) within 4 weeks before the start of treatment; 14.Patients with a history of psychotropic substance abuse and unable to quit or with a history of mental disorders; 15.Patients with massive pleural effusion or ascites accompanied by clinical symptoms or requiring symptomatic treatment; 16.Patients with a history of other malignant tumors within the past 5 years, except cured cutaneous basal cell carcinoma and cervical carcinoma in situ; patients with other early malignant tumors without systemic treatment who have not been found to have recurrence and metastasis more than 5 years after local radical treatment may be included if the bladder lesion is assessed and determined to be a non-metastatic lesion by the investigator. 17.Patients with other serious diseases, such as severe active infection 18.Other severe, acute, or chronic medical conditions or psychiatric disorders or laboratory abnormalities that, in the opinion of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results. 19.Patients who do not meet the physical conditions for radical surgery or refuse radical surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological Complete Response (pCR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Clinical complete response rate (cCR);Disease free survival (DFS);Progress free survival (PFS);Overall survival (OS);Cancer-specific survival rate;Adverse events rate;Completion rate of neoadjuvant combination therapy;Tumor downstaging rate; | — |
Countries
China
Contacts
Public ContactWei Qiang
West China Hospital, Sichuan University
Outcome results
None listed