Upper Urinary Tract Urothelial CarcinomaPhase 2NCT05160285
Neoadjuvant Nivolumab for Upper Tract Urothelial Carcinoma
A Phase 2 study testing Nivolumab 100 MG in 10 ML Injection in people with Upper Urinary Tract Urothelial Carcinoma, run by YULISU at 1 site in Taiwan.
Trial summary
The aim of this study is to explore efficacy and safety of neoadjuvant nivolumab for non-metastatic upper tract urothelial carcinoma (UTUC), and explore the potential predictive biomarkers of immunotherapy. Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Upper Urinary Tract Urothelial Carcinoma
- What is being tested?
- Nivolumab 100 MG in 10 ML Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteTaiwan
- Study dates
- 25 Dec 2020to 30 Dec 2024
- 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 20 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a histologically or clinically confirmed diagnosis of locally advanced (cT2-T4 and N0M0) urothelial carcinoma of the renal pelvis and/or ureter (UTUC). Pure urothelial carcinoma or urothelial carcinoma mixed with other histological variant are allowed, but urothelial carcinoma must be the predominant histology.
- Have at least a measurable lesion based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
- Voluntarily agree to participate by providing written informed consent/assent for the trial.
- Age (at the time of informed consent): 20 years and older
- Have received no prior systemic chemotherapy for advanced urothelial carcinoma, with the following exceptions:
- Platinum-based chemotherapy for previous a history of ipsilateral UTUC or bladder cancer in purpose of neoadjuvant or adjuvant treatment with recurrence > 6 months from completion of therapy is permitted.
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- Low-dose chemotherapy (e.g., low-dose cisplatin, cisplatin plus 5-FU, mitomycin plus 5-FU, or cisplatin plus paclitaxel) given concurrently with radiation to urothelial carcinoma of bladder is not considered systemic therapy.
- Have willing to provide tissue for exploratory biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion from the renal pelvis or ureter tumor.
- Have an ECOG PS of 0, 1, or 2.
- Have adequate organ function as defined in Table 6. (All screening labs should be performed within 3 weeks prior to treatment initiation.)
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 7.5.2 - Contraception, for the course of the trial through 5 months or more after the last dose of nivolumab
Who cannot join
- 1. Is currently participating and receiving study therapy or investigational agents. Patients who withdraw of previous clinical trials should have a 4-weeks washout period of investigational drug before participating this study.
- 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
- 3. Has an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Short-term (<7 days) use of systemic corticosteroids is allowed when use is considered SOC.
- Subjects with vitiligo, type I diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy would be an exception to this rule.
- Subjects who require intermittent use of bronchodilators, inhaled steroids, or local steroid injections would not be excluded from the trial.
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- 4. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
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- Exceptions include basal cell carcinoma of the skin; squamous cell carcinoma of the skin that has undergone potentially curative surgery; in situ cervical cancer; early stage of prostate cancer (stage 1) with low Gleason score ≤6; and prostate-specific antigen (PSA) undetectable.
- A history of urothelial carcinoma, including upper tract urothelial carcinoma or bladder cancer who received curative-intent surgery (nephroureterectomy, segmentectomy, TURBT, partial cystectomy, radical cystoprostectomy) > 12 months before first-dose trial treatment will be the exception.
- 5. Has a history of (non-infectious) pneumonitis or interstitial lung disease or pulmonary fibrosis diagnosed based on imaging (CT of chest preferably).
- 6. Has active tuberculosis (TB) (Bacillus tuberculosis). 7. Has an active infection requiring systemic therapy within 7 days prior to the first dose of trial treatment.
- 8. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 5 months or more after the last dose of nivolumab.
- 9. Has a history of uncontrolled or significant cardiovascular disease meeting any of the following:
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- Myocardial infarction within 180 days before first-dose of trial treatment
- New York Heart Association (NYHA) class III or IV congestive heart failure
- Myocarditis, no matter what etiology should be excluded
- Arrhythmia requiring treatment (e.g. atrial fibrillation/flutter, ventricular tachycardia or fibrillation, paroxysmal supraventricular tachycardia, symptomatic bradycardia, sick sinus syndrome or high-grade atrioventricular block).
- Has permanent pacemaker implantation or implantable cardioverter defibrillator (ICD).
- 10. Has received prior therapy with an anti-PD-1, or anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
- 11. Has undergone major surgery (any surgery involving general anesthesia) within 28 days before first-dose of study therapy.
- 12. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- 13. Has known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected). Controlled (treated) hepatitis B subject will be allowed if they meet the following criteria:
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- Antiviral therapy for HBV must be given for at least 8 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug.
- Subject who are anti-HBc (+), negative for HBsAg, negative for anti-HBs and have an HBV viral load under 100 IU/mL don't need HBV anti-viral prophylaxis.
- 14. Has received a live virus vaccine within 30 days of planned start of trial therapy.
- 15. Has known CNS metastases and/or leptomeningeal carcinomatosis. 16. Has symptomatic ascites or pleural effusion. 17. Has had a prior allogeneic stem cell or bone marrow transplant. 18. Has received any unapproved or unlicensed drug (e.g. marketed drugs unapproved for urothelial carcinoma, investigational use of drugs, herb combination) within 28 days before first-dose of study drug.
- 19. Are otherwise unfit for the study in the investigator's or sub-investigator's opinion.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 833
Yu-Li Su, MD, +886-975056834, yolisu@cgmh.org.tw
Chien-Ya Lin, RPN, +886-7-7317123 ext. 3681, chanyai0725@cgmh.org.tw
About this study
Official title: The NEVOLUTION Study: An Open Label, Single-arm, Phase II Study of Neoadjuvant Nivolumab in Locally Advanced Upper Tract Urothelial Carcinoma
The aim of this study is to explore efficacy and safety of neoadjuvant nivolumab for non-metastatic upper tract urothelial carcinoma (UTUC), and explore the potential predictive biomarkers of immunotherapy.
Read the detailed description
Upper urinary tract urothelial carcinoma (UTUC) is a malignant tumor originated from the epithelium of upper urinary tract (renal pelvis and ureter). The standard treatment of UTUC is radical nephroureterectomy with ipsilateral bladder cuff excision. For locally advanced disease, neoadjuvant chemotherapy or adjuvant chemotherapy with radiotherapy is also a considerable treatment. In general, patients with UTUC are often diagnosed in a late stage with a poor survival.
Nowadays, immune checkpoint inhibitor (ICI) emerged huge success in treatment of various type of cancers, including metastatic urothelial carcinoma. Several anti-PD1 or PD-L1 agents demonstrated an exciting response for metastatic urothelial carcinoma. The encouraging success makes clinical trials moving forward to neoadjuvant setting. In the PURE-01 study, patients with muscle-invasive bladder cancer received 3 cycles of neoadjuvant pembrolizumab achieving 39.5% pathological complete response (pCR). It brought a brand-new hope for organ-preservation treatment strategy. So far, neoadjuvant ICI has not been tested in patients with UTUC, irrespective for treatment efficacy or safety analysis. More importantly, there is still lack of reliable biomarkers to predict treatment response of ICI, which definitely an unmet medical need in clinical practice.
Therefore, the investigators proposed a phase II, open-label study of neoadjuvant nivolumab in locally advanced UTUC. Investigators believe that neoadjuvant nivolumab will achieve at least similar pCR rate compared with neoadjuvant pembrolizumab in UCB patients. Furthermore, investigators will conduct a comprehensive exploratory genomic analysis to identify the potential candidate biomarkers to predict the response of nivolumab.
- Conditions
- Upper Urinary Tract Urothelial Carcinoma
- Being tested
- Nivolumab 100 MG in 10 ML Injection
- Keywords
- upper tract urothelial carcinoma, immune checkpoint inhibitor, neoadjuvant treatment, pathological complete response, whole exome sequencing, biomarker, RNA sequencing, ctDNA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab 100 MG in 10 ML InjectionDrug
If you meet all the conditions to participate in the trial, you will receive the following treatments: Your physician will give you 360 mg of Nivolumab as an intravenous infusion every 3 weeks for about 30 minutes. For safety reasons, we recommend that you stay in the hospital for 60 minutes after the initial infusion of nivolumab. There will be a total of 3 cycles of Nivolumab treatments during the study period. You will need to return every 3 weeks. Each return will collect about 50 ml (10 tsp) of blood samples, depending on local standards.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant nivolumab treatment arm | Experimental | Nivolumab 360mg intravenous adminstration every 3 weeks Receives: Drug: Nivolumab 100 MG in 10 ML Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathologic complete response rate (pCR)
determined by genitourologic pathologist
Measured: 1 month post neoadjuvant nivolumab and surgery
Secondary outcomes (5)
Treatment related adverse effect
determined by CTCAE
Measured: 3 months during nivolumab treatment
Surgical complication
determined by Clavien-Dindo classification
Measured: 1 month within surgery
Objective response rate
determined by RECIST 1.1 criteria
Measured: 3 months
Disease free survival
Milestone time points analysis of DFS6, DFS12, DFS 18 and median PFS by investigator assessment per RECIST 1.1
Measured: 6 months
Overall survival
Milestone time points analysis of OS6, OS12, OS18 and median OS by investigator assessment per RECIST 1.1
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2021
- Study start25 Dec 2020
- Primary completion15 Dec 2023 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Upper Urinary Tract Urothelial CarcinomaStudies of the same condition, open and under way.
- 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
- Open Label, Single-arm, Phase II Study
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- YULISU
- Sponsor type
- University, hospital or other
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Responsible party
- Sponsor-investigator, YULISU, Chang Gung Memorial Hospital
- Investigators
- Yu-Li Su, MD, Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05160285
- Sponsor's protocol ID
- KCGMHCTC-2019005
- Other IDs
- CPRPG8J0011
- Status last verified
- Dec 2021
- First submitted
- 24 Dec 2020
- Last updated
- 16 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NEVOLUTION Study: An Open Label, Single-arm, Phase II Study of Neoadjuvant Nivolumab in Locally Advanced Upper Tract Urothelial Carcinoma
- ClinicalTrials.gov ID
- NCT05160285
- Acronym / sponsor ID
- KCGMHCTC-2019005
- Conditions
- Upper Urinary Tract Urothelial Carcinoma
- Keywords
- upper tract urothelial carcinoma, immune checkpoint inhibitor, neoadjuvant treatment, pathological complete response, whole exome sequencing, biomarker, RNA sequencing, ctDNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- YULISUUniversity, hospital or other
- Collaborators
- Ono Pharmaceutical Co., Ltd.
- Study start
- 25 Dec 2020 (actual)
- Primary completion
- 15 Dec 2023 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 16 Dec 2021 (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.
The aim of this study is to explore efficacy and safety of neoadjuvant nivolumab for non-metastatic upper tract urothelial carcinoma (UTUC), and explore the potential predictive biomarkers of immunotherapy.
Detailed description
Upper urinary tract urothelial carcinoma (UTUC) is a malignant tumor originated from the epithelium of upper urinary tract (renal pelvis and ureter). The standard treatment of UTUC is radical nephroureterectomy with ipsilateral bladder cuff excision. For locally advanced disease, neoadjuvant chemotherapy or adjuvant chemotherapy with radiotherapy is also a considerable treatment. In general, patients with UTUC are often diagnosed in a late stage with a poor survival.
Nowadays, immune checkpoint inhibitor (ICI) emerged huge success in treatment of various type of cancers, including metastatic urothelial carcinoma. Several anti-PD1 or PD-L1 agents demonstrated an exciting response for metastatic urothelial carcinoma. The encouraging success makes clinical trials moving forward to neoadjuvant setting. In the PURE-01 study, patients with muscle-invasive bladder cancer received 3 cycles of neoadjuvant pembrolizumab achieving 39.5% pathological complete response (pCR). It brought a brand-new hope for organ-preservation treatment strategy. So far, neoadjuvant ICI has not been tested in patients with UTUC, irrespective for treatment efficacy or safety analysis. More importantly, there is still lack of reliable biomarkers to predict treatment response of ICI, which definitely an unmet medical need in clinical practice.
Therefore, the investigators proposed a phase II, open-label study of neoadjuvant nivolumab in locally advanced UTUC. Investigators believe that neoadjuvant nivolumab will achieve at least similar pCR rate compared with neoadjuvant pembrolizumab in UCB patients. Furthermore, investigators will conduct a comprehensive exploratory genomic analysis to identify the potential candidate biomarkers to predict the response of nivolumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open Label, Single-arm, Phase II Study
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant nivolumab treatment arm | Experimental | Drug: Nivolumab 100 MG in 10 ML InjectionNivolumab 360mg intravenous adminstration every 3 weeks |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Have a histologically or clinically confirmed diagnosis of locally advanced (cT2-T4 and N0M0) urothelial carcinoma of the renal pelvis and/or ureter (UTUC). Pure urothelial carcinoma or urothelial carcinoma mixed with other histological variant are allowed, but urothelial carcinoma must be the predominant histology.
- Have at least a measurable lesion based on RECIST 1.1 as determined by the local site investigator/radiology assessment.
- Voluntarily agree to participate by providing written informed consent/assent for the trial.
- Age (at the time of informed consent): 20 years and older
- Have received no prior systemic chemotherapy for advanced urothelial carcinoma, with the following exceptions:
Key exclusion criteria (30 listed)
- 1. Is currently participating and receiving study therapy or investigational agents. Patients who withdraw of previous clinical trials should have a 4-weeks washout period of investigational drug before participating this study.
- 2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
- 3. Has an 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- 4. Has a known additional malignancy that is progressing or requires active treatment within the past 5 years.
- <!-- -->
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 |
|---|---|---|
| Nivolumab 100 MG in 10 ML InjectionIf you meet all the conditions to participate in the trial, you will receive the following treatments: Your physician will give you 360 mg of Nivolumab as an intravenous infusion every 3 weeks for about 30 minutes. For safety reasons, we recommend that you stay in the hospital for 60 minutes after the initial infusion of nivolumab. There will be a total of 3 cycles of Nivolumab treatments during the study period. You will need to return every 3 weeks. Each return will collect about 50 ml (10 tsp) of blood samples, depending on local standards. | Drug | Neoadjuvant nivolumab treatment arm |
Primary outcome
pathologic complete response rate (pCR)
Time frame: 1 month post neoadjuvant nivolumab and surgery
determined by genitourologic pathologist
5 secondary outcomes
Treatment related adverse effect
Time frame: 3 months during nivolumab treatment
Surgical complication
Time frame: 1 month within surgery
Objective response rate
Time frame: 3 months
Disease free survival
Time frame: 6 months
Overall survival
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2021.
- Individual participant dataSharing planned: No
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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.
Yu-Li Su, MD principal investigator
Chang Gung Memorial Hospital
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 Nivolumab 100 MG in 10 ML Injection in people with Upper Urinary Tract Urothelial Carcinoma, run by YULISU at 1 site in Taiwan.
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 12 inclusion and 30 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 16 Dec 2021. 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 Taiwan. 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?
Contact Yu-Li Su, MD (+886-975056834, yolisu@cgmh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathologic complete response rate (pCR) (time frame: 1 month post neoadjuvant nivolumab and 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 16 Dec 2021.