Neoadjuvant Therapy of Locally Advanced Upper Urinary Tract Urothelial CarcinomaPhase 2NCT04672317
Neoadjuvant PD-1 Monoclonal Antibody Plus Cisplatin-based Chemotherapy in Locally Advanced Upper Tract Urothelial Carcinoma
A Phase 2 study testing Immunotherapy combined with chemotherapy in people with Neoadjuvant Therapy of Locally Advanced Upper Urinary Tract Urothelial Carcinoma, run by RenJi Hospital at 1 site in China.
Trial summary
This study is designed prospectively to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Neoadjuvant Therapy of Locally Advanced Upper Urinary Tract Urothelial Carcinoma
- What is being tested?
- Immunotherapy combined with chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 10 Dec 2020to 1 Jun 2022
- 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. 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 nephrectomy by an attending urologist; 2. Patients who have a clinical stage of 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 and AST≤2.5×ULN；eGFR ≥ 60ml/min (MdRD) 6. Agree to comply with scheduled visits, treatment plans, lab tests and any other required study procedures;
Who cannot join
- Patients who has received prior therapy of an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody;
- Patients who are allergic to monoclonal antibodies or any of its excipients;
- Patients who have received other anti-tumor treatment (e. g., Steroid therapy, immunotherapy) within 4 weeks or enrolled in other clinical trials;
- Patients who are pregnant or breastfeeding, or expecting to conceive;
- Patients who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies);
- Patients who have known active Hepatitis B or Hepatitis C;
Show all 15Show fewer
- Patients who have active autoimmune disease that has required systemic treatment in the past 2 years;
- Patients who have received a live vaccine within 30 days prior to the first dose of trial treatment;
- Patients who have received prior radiation therapy to the bladder;
- Patients who have bladder cancer;
- Patients who have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
- Patients who have a history of substance abuse or with a history of mental disorders;
- 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 or low-risk prostate cancer, etc;Patients who have active tuberculosis;
- 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);
- Patients who have a large amount of pleural fluid or ascites with clinical symptoms or requiring symptomatic treatment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Open Clinical Study to Examine the Efficacy and Safety of Neoadjuvant Tislelizumab Combined With Cisplatin-based Chemotherapy in Patients With Locally Advanced Upper Urinary Tract Urothelial Carcinoma
This study is designed prospectively to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC). 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 in combination with cisplatin-based chemotherapy 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 combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC).
- Being tested
- Immunotherapy combined with chemotherapy
- Keywords
- neoadjuvant therapy, radical nephroureterectomy, Tislelizumab, chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunotherapy combined with chemotherapyDrug
Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before radical nephroureterectomy and lymphadenectomy.
Drug: Tislelizumab 200 mg per cycle, IV on day 14 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy
Other Names:
- anti-PD-1 monoclonal antibody Drug: Cisplatin 70mg/m2 IV on day 2of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy. Dose fractionation is permissible.
Drug: Gemcitabine 1000mg/m2 IV on day 1 and Day 8 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant arm | Experimental | Patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before radical nephroureterectomy and lymphadenectomy.
Drug: Tislelizumab 200 mg per cycle, IV on day 14 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy Drug: Cisplatin 70mg/m2 IV on day 2of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy. Dose fractionation is permissible.
Drug: Gemcitabine 1000mg/m2 IV on day 1 and Day 8 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy Receives: Drug: Immunotherapy combined with chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response rate
the absence of visible lesion of carcinoma (ypT0/Tis) and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen
Measured: 30 days after surgery
Secondary outcomes (1)
Pathologic response rate
The rate of patients that reach pathological downstaging at the time of nephroureterectomy.
Measured: 30 days after surgery
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 start10 Dec 2020
- Primary completion1 Jun 2022 (estimated)
- Study completion1 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoadjuvant Therapy of Locally Advanced 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
- Before surgery, patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT04672317
- Sponsor's protocol ID
- UTUC-NEOCI
- Status last verified
- Dec 2020
- First submitted
- 12 Dec 2020
- Last updated
- 17 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open Clinical Study to Examine the Efficacy and Safety of Neoadjuvant Tislelizumab Combined With Cisplatin-based Chemotherapy in Patients With Locally Advanced Upper Urinary Tract Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT04672317
- Acronym / sponsor ID
- UTUC-NEOCI
- Keywords
- neoadjuvant therapy, radical nephroureterectomy, Tislelizumab, chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (actual)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 10 Dec 2020 (actual)
- Primary completion
- 1 Jun 2022 (estimated)
- Study completion
- 1 Jun 2022 (estimated)
- 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.
This study is designed prospectively to investigate the safety and efficacy of neoadjuvant PD-1 monoclonal antibody combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC). 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 in combination with cisplatin-based chemotherapy 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 combined with cisplatin-based chemotherapy in patients with locally advanced upper urinary tract urothelial carcinoma (UTUC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Before surgery, patients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant arm | Experimental | Drug: Immunotherapy combined with chemotherapyPatients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before radical nephroureterectomy and lymphadenectomy. Drug: Tislelizumab 200 mg per cycle, IV on day 14 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy Drug: Cisplatin 70mg/m2 IV on day 2of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy. Dose fractionation is permissible. Drug: Gemcitabine 1000mg/m2 IV on day 1 and Day 8 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 nephrectomy by an attending urologist; 2. Patients who have a clinical stage of 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;
Key exclusion criteria (15 listed)
- Patients who has received prior therapy of an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody;
- Patients who are allergic to monoclonal antibodies or any of its excipients;
- Patients who have received other anti-tumor treatment (e. g., Steroid therapy, immunotherapy) within 4 weeks or enrolled in other clinical trials;
- Patients who are pregnant or breastfeeding, or expecting to conceive;
- 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 |
|---|---|---|
| Immunotherapy combined with chemotherapyPatients will receive 2-4 cycles of Tislelizumab (200mg per cycle) in combination with cisplatin-based chemotherapy before radical nephroureterectomy and lymphadenectomy. Drug: Tislelizumab 200 mg per cycle, IV on day 14 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy Other Names: • anti-PD-1 monoclonal antibody Drug: Cisplatin 70mg/m2 IV on day 2of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy. Dose fractionation is permissible. Drug: Gemcitabine 1000mg/m2 IV on day 1 and Day 8 of every 3-week cycle, for 2-4 cycles prior to radical nephroureterectomy and lymphadenectomy | Drug | Neoadjuvant arm |
Primary outcome
Pathological complete response rate
Time frame: 30 days after surgery
the absence of visible lesion of carcinoma (ypT0/Tis) and the absence of microscopic lymph node metastases (ypN0) on the final surgical specimen
1 secondary outcome
Pathologic response rate
Time frame: 30 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
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 Immunotherapy combined with chemotherapy in people with Neoadjuvant Therapy of Locally Advanced 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 4 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: status not confirmed, as of the sponsor's last update on 17 Dec 2020. 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?
Results are not available in the source record.
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 complete response 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?
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 17 Dec 2020.