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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tislelizumab and Nab-Paclitaxel | Experimental | Tislelizumab 200mg IV on day 1 in combination with nab-paclitaxel 200mg IV on day 2 every 3 weeks for 3 or 4 cycles followed by transurethral resection biopsy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tislelizumab | Drug | Tislelizumab 200mg will be administered on Day 1 of each cycle for 4 treatment cycles. |
|
| Measure | Description | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Cystectomy-Free Survival (CFS) | defined from D1 of treatment until cystectomy. | up to 3 years |
| Duration of Response (DOR) | up to 3 years |
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Inclusion Criteria:
Willing and able to provide written informed consent;
Ability to comply with the protocol;
Age ≥ 18 years;
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);
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;
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;
Agreed to provide tissue examination samples (for detection of PD-L1 expression, tumor mutation load, IHC, detection of DNA and RNA, etc;)
Organ function level must meet the following requirements:
The subjects volunteered to join the study, signed informed consent, and had good compliance with follow-up;
Exclusion Criteria:
Receive live attenuated vaccine within 4 weeks before treatment or during the study period;
Active, known or suspected autoimmune diseases;
History of primary immunodeficiency;
Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
Pregnant or lactating female patients;
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;
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);
Known or suspected allergy to tislelizumab and albumin paclitaxel;
Have a clear history of active tuberculosis;
Received PD-1 / PD-L1 / CTLA-4 antibody or other immunotherapy in the past;
Participating in other clinical researchers;
Men with reproductive capacity or women who are likely to become pregnant do not take reliable contraceptive measures;
Uncontrolled concurrent diseases, including but not limited to:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hailong Hu, MD,PhD | Contact | +86-13662096232 | hhllove2004@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Hailong Hu, MD,PhD | Tianjin Medical University Second Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Medical University Second Hospital | Recruiting | Tianjin | Tianjin Municipality | 300211 | China |
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| Nab-paclitaxel | Drug | Nab-paclitaxel 200mg will be administered on Day 2 of each cycle for 4 treatment cycles. |
|
| Number of adverse events and severity by grade (CTCAE) | 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). | 12 weeks of treatment plus 30 days for toxicity followup |
| ID | Term |
|---|---|
| C000707970 | tislelizumab |
| C520255 | 130-nm albumin-bound paclitaxel |
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