Clinical trial NCT04909775: Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer
Official title: A Prospective, Single Center Clinical Study to Examine Cisplatin-based Chemotherapy Combined With Tislelizumab as Bladder Sparing Treatment for Patients With Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Muscle-Invasive Bladder Carcinoma
Keywords: Bladder sparing treatment
muscle invasive bladder cancer
Tislelizumab
immunotherapy
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2021-06-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Cisplatin-based chemotherapy combined with tislelizumab
Primary purpose: TREATMENT

Brief summary: This study is designed prospectively to investigate the safety, efficacy and feasibility of cisplatin-based chemotherapy combined with tislelizumab as bladder sparing treatment for patients with muscle invasive bladder cancer (MIBC) which are eligible for cisplatin. The patients that achieved clinical remission after 4 cycles of cisplatin/gemcitabine and tislelizumab, will receive tislelizumab maintenance therapy for a year or 13 cycles. Tislelizumab, an anti-programmed death protein-1 (PD-1) monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The safety, tolerability, and efficacy of tislelizumab in patients with PD-L1 positive urothelial carcinoma who progressed during/following platinum-containing therapy was proved in a phase 2 trial (CTR20170071).

This trial investigates the efficacy of cisplatin-based chemotherapy combined with Tislelizumab to induce clinical complete remission of muscle invasive bladder cancer and the feasibility to provide bladder sparing treatment for these patients.

Detailed description: The patients that meet the Inclusion and Exclusion Criteria will treat with 4 cycles of cisplatin-based chemotherapy combined with Tislelizumab (200mg per cycle) prior to cystectomy discussion. The patients that show clinical benefit will receive tislelizumab for bladder sparing. Forty patients will be enrolled in this trial.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 and ≤75 years old on day of signing informed consent
* Signing informed consent
* Patients with histologically confirmed muscle-invasive bladder cancer (cT2-T4, N0, M0) and with strong intent to bladder sparing(Patients with mixed histology, predominantly transitional cells, could be enrolled. )
* Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 15 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available.
* ECOG performance status of 0 or 1
* Adequate organ and marrow function for cisplatin treatment
* No received prior therapy with systemic chemotherapy or immunotherapy

Exclusion Criteria:

* Received prior therapies targeting PD-1, PD-L1, PD-L2, CTLA4, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
* Any approved anticancer therapy within 28 days before enrollment
* Active leptomeningeal disease or uncontrolled, untreated brain metastasis
* Participants with uncontrolled hypercalcemia
* Participants with active autoimmune diseases or history of autoimmune diseases that may relapse
* History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled diseases
* A known history of HIV infection
* Prior allogeneic stem cell transplantation or organ transplantation
* History of severe hypersensitivity reactions to other monoclonal antibodies
* History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds

Primary outcomes:
measure: Clinical complete remission rate (cCR)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Duration of cCR
timeFrame: Up to 24 months
measure: Bladder-intact event-free survival (BI-EFS)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Danfeng Xu
role: PRINCIPAL_INVESTIGATOR
References: