Neoadjuvant PD-1 Monoclonal Antibody in Locally Advanced Upper Tract Urothelial Carcinoma

Sponsor

RenJi Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04672330

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Neoadjuvant therapy of cisplatin-based chemotherapy has been proved to improve prognosis of muscle invasive UTUC patients in several studies. This study is designed to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC) which are ineligible for cisplatin. 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 focuses on the efficacy of Tislelizumab to induce pathological down-staging of locally advanced UTUC in neoadjuvant setting.

Condition or Disease	Intervention/Treatment	Phase
Neoadjuvant Immunotherapy of Locally Advanced Upper Urinary Tract Urothelial Carcinoma	Drug: Tislelizumab	Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to radical nephroureterectomy and lymphadenectomyPatients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to radical nephroureterectomy and lymphadenectomy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Open, Single-center Clinical Study to Examine the Efficacy and Safety of Neoadjuvant Tislelizumab in Patients With Locally Advanced Upper Urinary Tract Urothelial Carcinoma

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant arm Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to radical nephroureterectomy and lymphadenectomy. Drug: Tislelizumab 200 mg per cycle, IV on day 1 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy	Drug: Tislelizumab Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) before radical nephroureterectomy and lymphadenectomy. Other Names: anti-PD-1 monoclonal antibody

Arm

Intervention/Treatment

Experimental: Neoadjuvant arm

Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to radical nephroureterectomy and lymphadenectomy. Drug: Tislelizumab 200 mg per cycle, IV on day 1 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy

Drug: Tislelizumab

Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) before radical nephroureterectomy and lymphadenectomy.

Other Names:

anti-PD-1 monoclonal antibody

Outcome Measures

Primary Outcome Measures

pathologic response rate [30 days after surgery]
Pathologic response rate include complete pathological remission（pT0N0）and partial pathological remission (≤pT1N0).

Secondary Outcome Measures

Pathologic downstaging response rate [30 days after surgery]
the rate of pT0-2N0 disease on the final surgical specimen and radiological staging
perioperative complication rate [30 days after surgery]
the rate of perioperative complications are determined according to Clavien classification
the completion rate of neoadjuvant therapy [120 days before surgery]
the rate of patients that complete all the neoadjuvant therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Patients that are identified as locally advanced upper urinary tract urothelial carcinoma by ureteroscopic biopsy and imaging diagnosis and are determined as appropriate candidates for radical nephrectomyby an attending urologist; 2. Has clinical stage T3-T4, any N, M0 or any T, N1-2, M0; 3. ECOG performance status of 0 to 2; 4. Adequate organ function defined by study-specified laboratory tests; Hemoglobin ≥90 g/L; Hematological Absolute neutrophil count (ANC) ≥1.5×109 /L; Platelets ≥100×109 /L 5. No functional organic disease: T-BIL≤1.5×upper limit of normal (ULN); ALT andAST≤2.5×ULN; Serum creatinine≤2×ULN; endogenous creatinine clearance rate>30ml/min

Agree to comply with scheduled visits, treatment plans, lab tests and any other required study procedures; 7. Patients who are ineligible for cisplatin for some reasons, for example endogenous creatinine clearance rate<60ml/min, patients refuse to receive cisplatin-based chemotherapy.

Exclusion Criteria:

1. Patients who have received prior therapy of an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody; 2. Patients who are allergic to monoclonal antibodies or any of its excipients;

Patients who have received other systems for anti-tumor treatment (e. g., Steroid therapy, immunotherapy) within 4 weeks or enrolled in other clinical trials; 4. Patients who are pregnant or breastfeeding, or expecting to conceive; 5. Patients who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies); 6. Patients who have known active Hepatitis B or Hepatitis C; 7. Patients who have active autoimmune disease that has required systemic treatment in the past 2 years; 8. Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment; 9. Patients who have received prior radiation therapy to the bladder; 10. Patients who have bladder cancer;
Patients who have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation; 12. Patients who have a history of substance abuse or with a history of mental disorders; 13. Patients who had other malignant tumors in the past five years that have not recovered except for curable tumors that have been cured including basal or squamous skin cancer, localized carcinoma in situ of the cervix or the breast and low-risk prostate cancer, etc.
Patients who have active tuberculosis; 15. Patients who have other serious and uncontrollable accompanying diseases that may affect compliance or interfere with the interpretation of results including active opportunistic infections or advanced (severe) infections, uncontrollable diabetes, cardiovascular disease (grade III or IV heart failure defined by the New York Heart Association classification, II degree atrioventricular block and above, myocardial infarction in the past 6 months, unstable arrhythmia or instability angina, cerebral infarction within 3 months, etc.) or lung disease (interstitial pneumonia, history of obstructive lung disease and symptomatic bronchospasm); 16. Patients who have a large amount of pleural fluid or ascites with clinical symptoms or requiring symptomatic treatment;