Clinical trial NCT04730219: Perioperative Tislelizumab Combined With Nab-Paclitaxel for Muscle-invasive Urothelial Bladder Carcinoma
Official title: An Open Label, Single-arm, Phase 2 Study of Perioperative Tislelizumab Combined With Nab-Paclitaxel Before Cystectomy or Complete TURBT for Patients With Muscle-invasive Urothelial Bladder Cancer.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Muscle Invasive Bladder Cancer
Urothelial Carcinoma
Keywords: neoadjuvant treatment
Lead sponsor: Tianjin Medical University Second Hospital
Sponsor class: OTHER
First posted: 2021-01-29
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II study to determine the safety and efficacy of tislelizumab when given in combination with nab-paclitaxel as perioperative treatment in patients with muscle-invasive bladder cancer (MIBC) prior to cystectomy or complete TURBT. Patients will receive treatment with tislelizumab in combination with nab-paclitaxel every 3 weeks for 3 treatment cycles over 9 weeks followed by standard radical cystectomy or complete TURBT.


Eligibility criteria: Inclusion Criteria:

1. Willing and able to provide written informed consent.
2. Ability to comply with the protocol.
3. Age ≥ 18 years.
4. Suitable and planned for complete transurethral resection of bladder tumor or radical cystectomy
5. Histopathologically confirmed urothelial carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) urothelial cell pattern.
6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI). If the clinical stage is T2-4aN1-3M0, it must be judged by the investigator. If it is judged that radical surgery can still be performed, it can be included in the study.
7. Expected survival time is greater than 12 weeks.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 1 or 2.
9. Agree to provide tissue examination specimens (used to detect PD-L1 expression, tumor mutation burden, etc.)
10. The organ function level must meet the following requirements:

    * Hematological indicators: absolute neutrophil count ≥1.5×10\^9/L, platelet count ≥80×10\^9/L, hemoglobin ≥6.0 g/dL (can be maintained by symptomatic treatment);
    * Liver function: total bilirubin ≤ 1.5 times the upper limit of normal value, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal value, if there is intrahepatic transaminase ≤ 5 times the upper limit of normal value;
    * Renal function: creatinine ≤ 2 times the upper limit of normal, and creatinine clearance ≥ 30 ml/min;

Exclusion Criteria:

1. Receive live attenuated vaccines within 4 weeks before treatment or plan to receive live attenuated vaccines during the study period.
2. Active, known or suspected autoimmune diseases.
3. Known history of primary immunodeficiency.
4. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
5. Female patients who are pregnant or breastfeeding.
6. Untreated acute or chronic active hepatitis B or C infection. In the case of patients receiving antiviral therapy, the doctor will judge whether they are eligible for enrollment according to the individual conditions of the patient while monitoring the virus copy number.
7. Have used immunosuppressive drugs in the past 4 weeks before starting treatment, excluding nasal spray and inhaled corticosteroids or physiological doses of systemic steroids (that is, prednisolone or equivalent physiological doses of no more than 10 mg/day) Other corticosteroids).
8. Those who are known or suspected to be allergic to tislelizumab and nab paclitaxel.
9. Have a clear history of active tuberculosis.
10. Have received PD-1/PD-L1/CTLA-4 antibody or other immunotherapy in the past.
11. Those who are participating in other clinical research.
12. Reproductive men or women who are likely to become pregnant have not taken reliable contraceptive measures.
13. Uncontrolled concurrent diseases include but are not limited to:

    * HIV-infected persons (HIV antibody positive).
    * Serious infections that are active or poorly clinically controlled.
    * There are serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney diseases, uncontrolled hypertension \[ie refers to After drug treatment, it is still greater than or equal to CTCAE Grade 2 hypertension\]) evidence.
    * Active bleeding or new thrombotic disease.

Primary outcomes:
measure: Clinical Complete Response (cCR) rate
timeFrame: At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)
measure: Event-free survival (EFS)
timeFrame: up to 3 years
measure: Overall Survival (OS)
timeFrame: up to 3 years
measure: Disease-specific survival (DSS)
timeFrame: up to 3 years
measure: Number of adverse events and severity by grade (CTCAE)
timeFrame: up to 1 years
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Second Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Second Hospital
name: Hailong Hu, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: