Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial CarcinomaPhase 2NCT04672330
Neoadjuvant PD-1 Monoclonal Antibody in Cisplatin-ineligible High Risk Upper Tract Urothelial Carcinoma
A Phase 2 study testing Tislelizumab in people with Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma, run by RenJi Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma
- What is being tested?
- Tislelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2020to 25 Nov 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. had non-metastatic high risk UTUC and planed to receive surgery(defined as high grade UTUC either by endoscopic biopsy or urinary cytology and/or any invasive aspect on radiological examination and/or hydronephrosis );
- 2. were ineligible for cisplatin-based chemotherapy(defined as meeting at least one of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status 2, creatinine clearance 30-60 mL/min, grade ≥2 audiometric hearing loss, grade ≥2 peripheral neuropathy, or New York Heart Association Class III heart failure);
- 3. had not received any systemic anti-tumor therapy;
- 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
- 6. Agree to comply with scheduled visits, treatment plans, lab tests and any other required study procedures;
Who cannot join
- 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;
- 3. 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;
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- 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 muscle invasive bladder cancer;
- 11.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.
- 14.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);
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of Tislelizumab(T) as Neoadjuvant Treatment for Cisplatin-ineligible High Risk Upper Tract Urothelial Carcinoma (UTUC)
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.
Read the detailed description
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.
- Conditions
- Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma
- Being tested
- Tislelizumab
- Keywords
- neoadjuvant therapy, radical nephroureterectomy, Tislelizumab, Cisplatin-ineligible
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TislelizumabDrug
Also called anti-PD-1 monoclonal antibody
Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) before surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation）
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant arm | Experimental | Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation） Drug: Tislelizumab 200 mg per cycle, IV on day 1 of every 3-week cycle, for 2-4 cycles prior to surgery Receives: Drug: Tislelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathological reponse rate
ypT0N0 at surgical specimen，in the intention-to-treat population
Measured: 30 days after surgery
Secondary outcomes (5)
pathological response rate
ypT0 and ypT1 at surgical specimen，in the intention-to-treat population
Measured: 30 days after surgery
perioperative complication rate
the rate of perioperative complications are determined according to Clavien classification
Measured: 30 days after surgery
objective response rate
the proportion of patients with a confirmed complete response or partial response based on radiological examination before surgery per RECIST version 1.1
Measured: 12 months after drug treatment
disease free survival
from surgery to any kind of recurrence including tumour bed, first metastasis, or death from any cause
Measured: 5 years after surgery or treatment
overall survival
time from enrollment to death for any cause
Measured: 5 years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start1 Dec 2020
- Primary completion25 Jan 2023
- Study completion25 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation）
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04672330
- Sponsor's protocol ID
- NEO-IO
- Status last verified
- Jan 2024
- First submitted
- 12 Dec 2020
- Last updated
- 9 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang J, Cai X, Ng C, Luo Y, Chen Q, Wang Z, Qiao K, Kong W, Zhang J, Chen Y, Zhang W, Zhang J, Zhang D, Wu G, Chen H, Xue W. A Phase 2 Study of Tislelizumab as Neoadjuvant Treatment of Cisplatin-Ineligible High-Risk Upper Tract Urothelial Carcinoma. J Urol. 2025 Jun;213(6):739-752. doi: 10.1097/JU.0000000000004475. Epub 2025 Feb 25.
PubMed 39999445
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Tislelizumab(T) as Neoadjuvant Treatment for Cisplatin-ineligible High Risk Upper Tract Urothelial Carcinoma (UTUC)
- ClinicalTrials.gov ID
- NCT04672330
- Acronym / sponsor ID
- NEO-IO
- Conditions
- Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma
- Keywords
- neoadjuvant therapy, radical nephroureterectomy, Tislelizumab, Cisplatin-ineligible
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 25 Jan 2023 (actual)
- Study completion
- 25 Nov 2023 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation）
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant arm | Experimental | Drug: TislelizumabPatients will receive 2-4 cycles of Tislelizumab (200mg per cycle) prior to surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation） Drug: Tislelizumab 200 mg per cycle, IV on day 1 of every 3-week cycle, for 2-4 cycles prior to surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 1. had non-metastatic high risk UTUC and planed to receive surgery(defined as high grade UTUC either by endoscopic biopsy or urinary cytology and/or any invasive aspect on radiological examination and/or hydronephrosis );
- 2. were ineligible for cisplatin-based chemotherapy(defined as meeting at least one of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status 2, creatinine clearance 30-60 mL/min, grade ≥2 audiometric hearing loss, grade ≥2 peripheral neuropathy, or New York Heart Association Class III heart failure);
- 3. had not received any systemic anti-tumor therapy;
- 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
Key exclusion criteria (15 listed)
- 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;
- 3. 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TislelizumabAlso: anti-PD-1 monoclonal antibodyPatients will receive 2-4 cycles of Tislelizumab (200mg per cycle) before surgery（radical nephroureterectomy, segmental ureteral resection, endoscopic ablation） | Drug | Neoadjuvant arm |
Primary outcome
pathological reponse rate
Time frame: 30 days after surgery
ypT0N0 at surgical specimen，in the intention-to-treat population
5 secondary outcomes
pathological response rate
Time frame: 30 days after surgery
perioperative complication rate
Time frame: 30 days after surgery
objective response rate
Time frame: 12 months after drug treatment
disease free survival
Time frame: 5 years after surgery or treatment
overall survival
Time frame: 5 years after enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
- Derived from this study: PubMed 39999445Huang J, Cai X, Ng C, Luo Y, Chen Q, Wang Z, Qiao K, Kong W, Zhang J, Chen Y, Zhang W, Zhang J, Zhang D, Wu G, Chen H, Xue W. A Phase 2 Study of Tislelizumab as Neoadjuvant Treatment of Cisplatin-Ineligible High-Risk Upper Tract Urothelial Carcinoma. J Urol. 2025 Jun;213(6):739-752. doi: 10.1097/JU.0000000000004475. Epub 2025 Feb 25.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tislelizumab in people with Neoadjuvant Immunotherapy of Cisplatin-ineligible High Risk Upper Urinary Tract Urothelial Carcinoma, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathological reponse rate (time frame: 30 days after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04672330, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.