Bladder Sparing Treatment of Tislelizumab, Gemcitabine and Cisplatin for Patients With PD-L1 Positive Muscle Invasive Bladder Cancer

NCT05401279 | Unknown Phase 2

• 1 other identifier: TICIG
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II open label single-arm prospective study aiming to investigate the efficacy of PD-1 inhibitor Tislelizumab combined with conventional gemcitabine and cisplatin as bladder sparing treatment for patients with PD-L1 positive muscle invasive bladder carcinoma (T2-3N0M0).

Conditions

Urothelial Carcinoma Bladder; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Two-year bladder-intact disease-free survival rate

  Bladder-intact disease-free survival is defined as time from initiation of protocol therapy until the development of muscle-invasive bladder cancer recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death, or cystectomy.

  2 years

Secondary Outcomes (5)

• Adverse Events

  2 years

• Overall survival

  up to 5 years

• Metastasis-free survival

  up to 5 years

• Disease-free survival

  up to 5 years

• Disease specific survival

  up to 5 years

Study Arms (1)

Gemcitabine, Cisplatin and Tislelizumab

EXPERIMENTAL

Patients will receive transurethral resection or partial cystectomy to remove all visible tumors with no residual disease left. 2-4 weeks after the surgery, patients will receive 8 cycles of tislelizumab combined with 4-6 cycles of gemcitabine and cisplatin.

Drug: Tislelizumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Tislelizumab DRUG

Tislelizumab 200mg will be administered on Day 1 of each 21 day cycle for 8 21-day cycles.

Gemcitabine, Cisplatin and Tislelizumab

Gemcitabine DRUG

Gemcitabine 1000mg/m\^2 will be administered on Days 1 and 8 for four to six 21-day cycles.

Gemcitabine, Cisplatin and Tislelizumab

Cisplatin DRUG

Cisplatin 70mg\^m2 will be administered on Day 1 for four to six 21-day cycles.

Gemcitabine, Cisplatin and Tislelizumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed muscle-invasive urothelial cancer of the bladder within 60 days of study enrollment. Variant histology and cis are not allowed. Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (FFPE tissue block or 20 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available. The specimen must be assessed as PD-L1 positive by two pathologists using SP263 kit.
• Clinical stage T2-T3, N0, M0 urothelial bladder cancer.
• Deemed to not be a candidate for radical cystectomy by attending urologic oncologist or refuse radical cystectomy.
• Willing to receive maximal transurethral resection or partial cystectomy to remove all bladder tumors
• Be willing and able to provide written informed consent/assent for the trial.
• Have a performance status of 0 or 2 on the Eastern Cooperative Oncology Group Performance Scale.
• Demonstrate adequate organ function as defined below, all screening labs should be performed within 10 days of protocol enrollment.
• Absolute neutrophil count \>= 1,500 /mcL;
• Platelets \>= 100,000 /mcL;
• Hemoglobin \>= 9.0 g/dL;
• Serum creatinine \<=1.5 x upper limit of normal (ULN) or calculated creatinine clearance \>= 30 mL/min as calculated by Cockcrof-Gault formulae or by 24 hour urine collection;
• Serum total bilirubin \<=1.5 x ULN or direct bilirubin \<= ULN for subjects with total -bilirubin levels \> 1.5 x ULN;
• Aspartate aminotransferase and alanine aminotransferase \<= 1.5 x ULN;
• Albumin \>= 2.5 mg/dL;
• International normalized ratio or prothrombin time (PT) \<= 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or partial prothrombin time (PTT) is within therapeutic range of intended use of anticoagulants;

You may not qualify if:

• Has received prior radiation therapy or systemic chemotherapy for urothelial bladder cancer including neoadjuvant chemotherapy. Prior intravesical chemotherapy or intravesical immunotherapy is permissible, however, no prior intravesical therapy is permitted within 4 weeks of study enrollment; adjuvant therapy is not permitted.
• Has received prior pelvic radiation therapy.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to tislelizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Any prior history of invasive malignancy within the past 5 years except non-melanoma skin cancer, carcinoma in-situ, localized prostate cancer without biochemical recurrence following definitive treatment.
• Has other active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of Guillain-Barre Syndrome or Stevens-Johnson Syndrome
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Renji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, Shanghai Municipality, 200127, China

RECRUITING

MeSH Terms

Interventions

tislelizumab; Gemcitabine; Cisplatin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Wei Xue, PhD

  Renji Hospital, School of Medicine, Shanghai Jiao Tong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunze Xu, PhD

CONTACT

+8618801967501; rjxuyunze@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

Study Record Dates

• First Submitted: May 29, 2022
• First Posted: June 2, 2022
• Study Start: June 1, 2022
• Primary Completion: April 1, 2024
• Study Completion: May 1, 2025
• Last Updated: August 18, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)