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

NCT ID: NCT04909775

Last Updated: 2021-06-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-31
• Study Completion Date: 2023-07-31

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.

Conditions

Muscle-Invasive Bladder Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

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.

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

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

Interventions

Tislelizumab

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Other Intervention Names

anti-PD-1 monoclonal antibody; cis-platinum; Gemcitabine Hydrochloride

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Danfeng Xu

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital

Locations

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Danfeng Xu

Role: CONTACT

xdf12036@rjh.com.cn

(021)64370045 ext. 666062

Wenhao Lin

Role: CONTACT

lwh970808@163.com

+8618930458051

Facility Contacts

Danfeng Xu

Role: primary

xdf12036@rjh.com.cn

（021）64370045 ext. 666062

Wenhao Lin

Role: backup

lwh970808@163.com

+8618930458051

Other Identifiers

RJBS-001

Identifier Type: -

Identifier Source: org_study_id