CClinicalTrials.gg
Not yet recruitingNCT06364904Updated Feb 21, 2025

A Clinical Trail to Determine the Safety and Efficacy of the Combination of Tislelizumab With Cisplatin and Gemcitabine, With or Without Trilaciclib for Patients With Untreated Unresectable and Metastatic Urothelial Carcinoma.

A Phase 3 interventional study of Tislelizumab, Cisplatin, Gemcitabine and Trilaciclib and Tislelizumab, Cisplatin, Gemcitabine in Bladder Cancer, sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University. Not yet recruiting at 8 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-02-21.

Sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
210
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The aim of this study is to see whether the Trilaciclib is safe and effective in slowing down the growth of bladder cancer in patients while taking chemoimmunotherapy.

02

Conditions studied

  • Bladder Cancer

Keywords

  • Immune Checkpoint Inhibitor
  • CDK4/6 Inhibitor
  • Cisplatin
  • Tislelizumab
  • Gemcitabine
  • Trilaciclib
03

In context

Carcinoma, Transitional Cell

716 studies on the registry are indexed under Carcinoma, Transitional Cell; 201 are open to participants now.

This study's planned enrollment of 210 is above the median of 49 across 549 interventional studies indexed under Carcinoma, Transitional Cell.

Browse Carcinoma, Transitional Cell studies →

Lead sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University is the lead sponsor of 466 studies on the registry; 271 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Voluntarily participate in this study, able to provide written informed consent and can understand and agree to comply with the requirements of the study and schedule of assessments.
  2. Participants diagnosed histologically or cytologically with locally advanced or metastatic urothelial carcinoma (UC) of the renal pelvis, ureter, bladder, or urethra. Eligible subjects for inclusion are those with a mixed histologic type, as assessed by the investigator, with urothelial component >50% and plasmacytoid subtype \<10%. Patients with histologically confirmed and radiologically assessed locally advanced or metastatic urothelial carcinoma of the urinary tract.
  3. Participants judged by the investigator to be tolerant of platinum-based therapy. Participants intolerant to platinum chemotherapy must meet at least one of the following criteria: ECOG performance status >1 or Karnofsky performance status 60% to 70%; creatinine clearance less than 60 ml/min; hearing loss ≥ Grade 2 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5; peripheral neuropathy ≥ Grade 2 according to NCI-CTCAE version 5; New York Heart Association Class III or IV heart failure.
  4. Must provide surgical or biopsy tumor tissue samples, and concurrent submission of relevant pathology reports is required. Participants are able to submit fresh surgical tissue or submit pathology slides for examination.
  5. ECOG Performance Status 0 or 1
  6. The participants must have well-functioning organ systems, as measured by the following screening laboratory values (obtained within ≤14 days before enrollment):

    a. When screening for the following parameters, participants must not have used growth factor support within ≤14 days before sample collection: i. Neutrophil absolute count ≥ 1.5x10\^9/L ii. Platelets ≥ 90x10\^9/L iii. Hemoglobin ≥ 90g/L b. International normalized ratio or activated partial thromboplastin time ≤ 1.5 times the upper limit of normal (ULN) c. Calculated creatinine clearance ≥ 50 mL/min d. Serum total bilirubin ≤ 1.5×ULN (if Gilbert's syndrome or indirect bilirubin concentration indicates extrahepatic elevation, should be ≤ 3×ULN) e. AST, ALT, and alkaline phosphatase ≤ 2.5×ULN

  7. Women who are not pregnant or not of childbearing potential must be willing to use effective contraception during the study and for ≥120 days after the last dose of toripalimab monotherapy or chemotherapy (whichever occurs later). Additionally, they must have a negative urine or serum pregnancy test result within ≤7 days before enrollment. Non-sterilized men must be willing to use effective contraception during the study and for ≥120 days after the last dose of toripalimab monotherapy or chemotherapy (whichever occurs later).
  8. According to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, at least one participant with measurable lesions is required.
  9. Participants with an expected survival of ≥3 months.

Exclusion criteria

Exclusion Criteria:

  1. Known active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. For patients with previously treated brain metastases, enrollment is not allowed if there has been CNS disease stability for at least 4 weeks before the first dose of study treatment and discontinuation of corticosteroid therapy for brain metastases for at least 2 weeks before the start of study treatment.
  2. Prior treatment with therapies targeting PD-1, PD-L1, PD-L2, CTLA-4, or other agents specifically targeting T-cell co-stimulation or checkpoint pathways.
  3. Receipt of other approved systemic anticancer therapy or systemic immunomodulatory agents (including but not limited to interferons, interleukins, and tumor necrosis factor) within 28 days before enrollment.
  4. Prior radiotherapy for bladder cancer.
  5. Prior systemic treatment for tumors, except:

    1. For patients previously treated with systemic chemotherapy, a treatment-free interval of at least 12 months from the last treatment to the start of drug treatment.
    2. Local intravesical chemotherapy or immunotherapy, completed at least 1 week before the start of study treatment.
  6. Major surgery or significant trauma within 28 days before enrollment (placement of vascular access device and transurethral resection of bladder tumor [TURBT] are not considered major surgery).
  7. Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days before enrollment (HBV infection is excluded according to exclusion criterion 11).
  8. Receipt of live vaccines within 28 days before enrollment (seasonal injections of influenza vaccine are usually inactivated vaccines and are allowed. Nasal vaccines are live vaccines and are not allowed).
  9. Active autoimmune diseases requiring systemic treatment, as determined by the investigator, which could affect the safety of study treatment.
  10. Long-term use of high-dose steroids or other immunosuppressive agents, as determined by the investigator, which could affect the safety of study treatment.
  11. Known potassium, sodium, calcium abnormalities, or hypoalbuminemia, interstitial lung disease, non-infectious pneumonia, or other uncontrolled systemic diseases, including diabetes, hypertension, cardiovascular diseases (e.g., active cardiac disease within 6 months before enrollment, including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, and requiring medication for ventricular arrhythmias).
  12. Untreated chronic hepatitis B patients with HBV DNA ≥500 IU/mL (2500 copies/mL) or HBV carriers are not eligible. Note: Patients with inactive hepatitis B surface antigen carriers or stable active HBV infection (HBV DNA \<500 IU/mL [2500 copies/mL]) after continuous antiviral treatment can be enrolled. HBV DNA testing is performed only in patients positive for antibodies to the hepatitis B core antigen.
  13. Patients with active hepatitis C are not eligible. Patients who test negative for HCV antibodies during the screening period or, if positive, test negative for HCV RNA after positive HCV antibody testing can be enrolled. Only patients positive for HCV antibodies need HCV RNA testing.
  14. History of immune deficiency (including human immunodeficiency virus [HIV] positive, other acquired, congenital immunodeficiency diseases) or a history of allogeneic stem cell transplantation or organ transplantation.
  15. Known allergies to other monoclonal antibodies.
  16. Known allergies to any study drug or excipient.
  17. Patients with toxic side effects (due to any treatment) that have not returned to baseline or a stable level, unless the investigator does not believe that such toxic side effects may pose a safety risk (e.g., hair loss, neurologic symptoms, and specific laboratory abnormalities).
  18. Underlying medical conditions, alcohol/drug abuse, or dependence that may adversely affect the administration of study drug, interpretation of results, or lead to a high risk of treatment complications.
  19. Concurrent participation in another therapeutic clinical study.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
210 participants (estimated)

Study arms

  • Active comparator
    Gemcitabine plus Cisplatin

    During each 21 days study cycle(up to 6 cycles), all participants will receive: 1. Tislelizumab: Taken 1x time at d1 each cycle or until it is determined participant must stop the drug. 2. Gemcitabine: d1, d8 each cycle or until it is determined participant must stop the drug. 3. Cisplatin: d2 each cycle or until it is determined participant must stop the drug. Tislelizumab maintenance therapy:after chemoimmunotherapy, q3W until it is determined participant must stop the drug, or 2 years of treatment is completed.

    Drug: Tislelizumab, Cisplatin, Gemcitabine

  • Experimental
    Gemcitabine, Cisplatin plus Trilaciclib

    During each 21 days study cycle(up to 6 cycles), all participants will receive: 1. Tislelizumab: Taken 1x time at d1 each cycle or until it is determined participant must stop the drug. 2. Gemcitabine: d1, d8 each cycle or until it is determined participant must stop the drug. 3. Cisplatin: d2 each cycle or until it is determined participant must stop the drug. 4. Trilaciclib: d1, d2, d8 each cycle or until it is determined participant must stop the drug. Tislelizumab maintenance therapy:after chemoimmunotherapy, q3W until it is determined participant must stop the drug, or 2 years of treatment is completed.

    Drug: Tislelizumab, Cisplatin, Gemcitabine and Trilaciclib

Interventions

  • DrugTislelizumab, Cisplatin, Gemcitabine and Trilaciclib

    Chemoimmunotherapy: 1. Tislelizumab: 200mg, 1x time at d1 each cycle 2. Gemcitabine: 1000mg/ m2, in d1, d8 each cycle 3. Cisplatin: 70 mg/m2, in d2 each cycle 4. Trilaciclib: 240mg/m2, d1, d2, d8 each cycle Tislelizumab maintenance therapy: after chemoimmunotherapy, 200mg, q3W.

  • DrugTislelizumab, Cisplatin, Gemcitabine

    Chemoimmunotherapy: 1. Tislelizumab: 200mg, 1x time at d1 each cycle 2. Gemcitabine: 1000mg/ m2, in d1, d8 each cycle 3. Cisplatin: 70 mg/m2, in d2 each cycle Tislelizumab maintenance therapy: after chemoimmunotherapy, 200mg, q3W.

06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Progression-Free Survival(PFS)

    Progression free survival was determined from start date of treatment to date of progression for patients who progressed or date of death for patients who died without progressing. The observations of patients remaining alive and progression free were censored at the date of last disease evaluation. The Kaplan-Meier method was used to determine the median and 95% confidence interval.

    Time frame: 24 months

  2. Percentage of Participants With Incidence of Grade 3/4 Neutropenia

    The proportion of participant with neutrophils with values \< 1\*10\^9/L during treatment.

    Time frame: Within 28 days of initial dosing

Secondary outcomes

  1. Rate of ORR

    The responses rate (PR+CR) in participants based on imaging \[CT scan of chest, abdomen, and pelvis (or MRI of abdomen and pelvis with CT chest without contrast when appropriate)\]

    Time frame: 60 months

  2. overall survival (OS)

    OS was measured from the date the participant started study to death for any reason.

    Time frame: 60 months

  3. Safety and AE

    Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event using the Medical Dictionary for Regulatory Activities (MedDRA) terms and graded per NCI-CTCAE v5.0. Number and Grade of patients who had a surgery-related adverse event (surgery-related AE) will be measured according to the Clavien-Dindo classification.

    Time frame: 60 months

  4. Disease Control Rate(DCR)

    The responses rate (PR+CR+SD) in participants based on imaging \[CT scan of chest, abdomen, and pelvis (or MRI of abdomen and pelvis with CT chest without contrast when appropriate)\].

    Time frame: 60 months

  5. During Of Response(DOR)

    During Of Response(DOR) was measured from the date from the first evaluation of the tumor as CR or PR to the first evaluation as PD or death from any cause.

    Time frame: 60 months

  6. Biomarker Endpoint Analyses

    Patients' biomarkers in urine, blood, and tumor tissues (include CPS, TPS, TMB, Ki67, etc.) will be detected with the treatment of the combination of Tislelizumab with Cisplatin and Gemcitabine, with or without Trilaciclib in untreated unresectable and metastatic urothelial.

    Time frame: 60 months

07

Study locations

8 sites
  • Nanfang Hospital, Southern Medical University
    Guangzhou, Guangdong, China
    • Peng Wu, Ph.D · Contact
  • Sun Yat-sen Memorial Hospital
    Guangzhou, Guangdong, China
    • Wenlong Zhong, Ph.D · Contact
  • The First Affiliated Hospital of Sun Yat-sen University
    Guangzhou, Guangdong, China
    • Junxin Chen, Ph.D · Contact
  • The Third Affiliated Hospital of Sun Yat-sen University
    Guangzhou, Guangdong, China
    • Yun Luo, Ph.D · Contact
  • Zhujiang Hospital of Southern Medical University
    Guangzhou, Guangdong, China
    • Ebai Xu, Ph.D · Contact
  • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei, China
    • Zheng Liu, Ph.D · Contact
  • Hunan Cancer Hospital
    Changsha, Hunan, China
    • Yu Xie, Ph.D · Contact
  • Xiangya Hospital, Central South University
    Changsha, Hunan, China
    • Xiongbing Zu, Ph.D · Contact
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 21, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06364904
Lead sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Responsible party
Sponsor
First posted
Apr 15, 2024
Start date
Oct 2025 (estimated)
Primary completion
Apr 15, 2027 (estimated)
Completion
Apr 15, 2029 (estimated)
Last update
Feb 21, 2025

Study contacts

Wenlong Zhong, Ph.D
Contact
zhongwlong3@mail.sysu.edu.cn
020-81338949
Tianxin Lin, Ph.D
study chair · Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion