Perioperative Tislelizumab Combined With Nab-Paclitaxel for Muscle-invasive Urothelial Bladder Carcinoma

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.

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Urothelial Carcinoma; Muscle Invasive Bladder Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Nab paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Tianjin Medical University Second Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab and Nab Paclitaxel; Tislelizumab 200mg IV on day 1 in combination with nab paclitaxel 200mg IV on day 2 every 3 weeks for 3 cycles followed by surgery.	Drug: Tislelizumab; Tislelizumab 200mg will be administered on Day 1 every 3 weeks for 3 cycles; Other Names: BGB-A317; Drug: Nab paclitaxel; Nab paclitaxel 200mg will be administered on Day 2 every 3 weeks for 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Complete Response (cCR) rate	defined as the absence of tumor residual confirmed by surgery (RC-PLND or complete TURBT), negative urine cytology and no evidence of lymph nodes or distant metastasis on imaging.	At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	defined from D1 of neoadjuvant treatment until progression (in those who progress prior to surgery) or until recurrence (post-surgery) or until death as a result of any cause.	up to 3 years
Overall Survival (OS)	defined as the number of days from study entry to death. Individuals who are alive at last contact will be censored on the date of last contact.	up to 3 years
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).	up to 1 years
Objective response rate (ORR)	defined as the proportion of patients who have a partial or complete response to therapy.	At the time of complete transurethral resection of bladder tumor or radical cystectomy (within 12 weeks of the first dose of tislelizumab)
Disease-specific survival (DSS)	DSS was documented from the date of initial treatment till the date of the disease-related death.	up to 3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital
• Investigators: Principal Investigator: Hailong Hu, MD,PhD, Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2020
• Primary Completion (Anticipated): February 1, 2024
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Carcinoma; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: TRUCE-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No