High-Risk, Non-Muscle Invasive Bladder Urothelial Carcinoma
Conditions
Keywords
Tislelizumab, Nab-Paclitaxel
Brief summary
This is a phase II study to determine the safety and efficacy of tislelizumab when given in combination with nab-paclitaxel as treatment for patients with high-risk non-muscle-invasive bladder cancer (HR NMIBC) which is not completely resectable. Patients will receive treatment with tislelizumab in combination with nab-paclitaxel every 3 weeks for 4 treatment cycles over 12 weeks followed by transurethral resection biopsy.
Interventions
DRUGTislelizumab
Tislelizumab 200mg will be administered on Day 1 of each cycle for 4 treatment cycles.
DRUGNab-paclitaxel
Nab-paclitaxel 200mg will be administered on Day 2 of each cycle for 4 treatment cycles.
Sponsors
Tianjin Medical University Second Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide written informed consent; 2. Ability to comply with the protocol; 3. Age ≥ 18 years; 4. High-risk non-muscle-invasive urothelial carcinoma or high-risk non-muscle-invasive urothelial carcinoma as the main pathological component \> 50%, difined as following: a. T1 b. High-grade Ta c.Carcinoma in situ(CIS); 5. Multi-point biopsy of bladder shows there are more than 2 section and over 3 points of pathological specimens are diagnosed as above, meanwhile, the tumor has to be diagnosed as not completely resectable by at least 2 senior urologist; 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2; 7. Agreed to provide tissue examination samples (for detection of PD-L1 expression, tumor mutation load, IHC, detection of DNA and RNA, etc;) 8. Organ function level must meet the following requirements: * Hematological indexes: neutrophil count \>= 1.5x10\^9/L, platelet count \>= 80x10\^9/L, hemoglobin \>= 6.0 g/dl (can be maintained by blood transfusion); * Liver function: total bilirubin \<=1.5 ULN, alanine aminotransferase and aspartate aminotransferase \<=2.5 ULN; 9. The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up;
Exclusion criteria
1. Receive live attenuated vaccine within 4 weeks before treatment or during the study period; 2. Active, known or suspected autoimmune diseases; 3. History of primary immunodeficiency; 4. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 5. Pregnant or lactating female patients; 6. Untreated acute or chronic active hepatitis B or hepatitis C infection. Under the condition of monitoring the virus copy number of patients receiving antiviral treatment, doctors can judge whether they are in line with the patients' individual conditions; 7. Prior use of immunosuppressive drugs within 4 weeks prior to the start of treatment, excluding nasal and inhaled corticosteroids or physiological doses of systemic steroids (i.e. not more than 10 mg / day prednisolone or other corticosteroids with the same physiological dose); 8. Known or suspected allergy to tislelizumab and albumin paclitaxel; 9. Have a clear history of active tuberculosis; 10. Received PD-1 / PD-L1 / CTLA-4 antibody or other immunotherapy in the past; 11. Participating in other clinical researchers; 12. Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures; 13. Uncontrolled concurrent diseases, including but not limited to: * HIV infected (HIV antibody positive); * Severe infection in active stage or poorly controlled; * Evidence of serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[i.e. hypertension greater than or equal to CTCAE grade 2 after drug treatment\]); * Patients with active bleeding or new thrombotic disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Complete Response (CR) Rate for tilelizumab combined with nab-paclitaxel | At the time of transurethral resection biopsy (within 9 or 12 weeks of the first dose of tislelizumab) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cystectomy-Free Survival (CFS) | up to 3 years | defined from D1 of treatment until cystectomy. |
| Duration of Response (DOR) | up to 3 years | — |
| Number of adverse events and severity by grade (CTCAE) | 12 weeks of treatment plus 30 days for toxicity followup | Safety and toxicity will be characterized according to the reported adverse event (AE) profile using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0, as well as a patient questionnaire derived from the Patient Reported Outcomes (PRO)-CTCAE and Patient Reported Outcomes Measurement Information System (PROMIS). |
Countries
China
Contacts
Primary ContactHailong Hu, MD,PhD
Outcome results
None listed