Chemotherapy Combined With Tislelizumab as Bladder Sparing Option for Patients With Muscle Invasive Bladder Cancer

NCT04909775 | Unknown Phase 2

• 1 other identifier: RJBS-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Muscle-Invasive Bladder Carcinoma

Keywords

Bladder sparing treatment; muscle invasive bladder cancer; Tislelizumab; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Clinical complete remission rate (cCR)

  The clinical complete remission rate (cCR) was defined as the proportion of patients with clinically confirmed cT0 or cTa(AJCC Cancer Staging Manual,8th ed. 2017 edition ).The cT0 or cTa was assessed by cystoscopy examination at 12 weeks after the initiation of combination therapy. Two-sided Clopper-Pearson 95% confidence intervals were constructed to evaluate the accuracy of cCR.

  Up to 24 months

Secondary Outcomes (2)

• Duration of cCR

  Up to 24 months

• Bladder-intact event-free survival (BI-EFS)

  Up to 24 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients will receive 4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before cystectomy discussion. The patients reach clinical complete remission will receive tislelizumab maintenance therapy for a year or 13 cycles.

Drug: Tislelizumab; Drug: Cisplatin; Drug: Gemcitabine

Interventions

Tislelizumab DRUG

200 mg per cycle, IV on day 1 of 3-week

Also known as: anti-PD-1 monoclonal antibody

Arm 1

Cisplatin DRUG

70mg/m2 IV on Day 1 of 3-week, for 4 cycles. Dose fractionation is permissible.

Also known as: cis-platinum

Arm 1

Gemcitabine DRUG

1000mg/m2, Day 1 and Day 8 of 3-week, for 4 cycles

Also known as: Gemcitabine Hydrochloride

Arm 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Interventions

tislelizumab; spartalizumab; Cisplatin; Gemcitabine

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Danfeng Xu

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danfeng Xu

CONTACT

(021)64370045; xdf12036@rjh.com.cn

Wenhao Lin

CONTACT

+8618930458051; lwh970808@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cisplatin-based chemotherapy combined with tislelizumab

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: June 2, 2021
• Study Start: July 1, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: June 2, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)