Urothelial CarcinomaPhase 1TURANDOTNCT04871594
Pre-operative Immunotherapy in Stage II-III Urothelial Cancer
A Phase 1 study testing Nivolumab in people with Urothelial Carcinoma, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
Trial summary
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. This study can be adapted or expanded based on the results obtained. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urothelial Carcinoma
- What is being tested?
- Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesNetherlands
- Study dates
- 23 Aug 2021to 30 Dec 2024
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide informed consent
- Age ≥ 18 years
- Resectable muscle-invasive UC (upper urinary tract allowed), defined as:
- cT2-4aN0M0 OR
- cT1-4aN1-3M0
- World Health Organization (WHO) performance Status 0 or 1.
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- Urothelial cancer is the dominant histology (>70%).
- Formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks from diagnostic TUR available (or equivalent FFPE tumor specimens for upper tract tumors; at least two biopsy cores available).
- PD-L1 status must be determined using the 22C3 pharmDx test. Combined positivity score (CPS) must be >10.
- Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥1.0x109/L, Platelets ≥100 x109/L, Hemoglobin ≥5.5 mmol/L, GFR>30 ml/min as per Cockcroft-Gault formula, AST ≤ 1.5 x ULN, ALT ≤1.5 x ULN, Bilirubin ≤1.5 X ULN
- Negative pregnancy test (βHCG in blood or urine) for female patients of childbearing potential within 2 weeks prior to Day 1 Cycle 1.
- Highly effective contraception for both male and female subjects if the risk of conception exists. Female patients of childbearing potential must comply with contraception methods as requested by the study protocol.
Who cannot join
- Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.
- Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
- Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
- Known history of Human Immunodeficiency Virus infection or tuberculosis, or other active infection requiring therapy at the time of inclusion.
- Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
- Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of adverse events
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- Medical condition requiring the use of immunosuppressive medications, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) will be allowed.
- Use of other investigational drugs before study drug administration
- Malignancy, other than urothelial cancer, in the previous 2 years, with a high chance of recurrence (estimated >10%). Patients with low risk prostate cancer (defined as Stage T1/T2a, Gleason score ≤ 6, and PSA ≤ 10 ng/mL) who are treatment-naive and undergoing active surveillance are eligible.
- Pregnant and lactating female patients.
- Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
- Severe infections within 2 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias and unstable angina.
- Previous intravenous chemotherapy for bladder cancer. Prior low-dose sensitizing chemotherapy used for combined modality treatment, or radiation alone, is allowed if patients have recurred after an initial response. Patients with residual disease after (chemo)radiation for bladder cancer are not eligible.
- Patients in whom use of a colon segment for urinary diversion is planned.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Antoni van Leeuwenhoek ziekenhuis
Amsterdam, 1066 CX
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA
About this study
Official title: A Phase 1b Trial in Stage II-III Urothelial Cancer to Explore Pre-operative Immunotherapy
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. This study can be adapted or expanded based on the results obtained.
Read the detailed description
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients.
Urothelial cancer patients will be included that are diagnosed with either:
- cT2-4aN0M0 OR
- cT1-4aN1-3M0
PD-L1 status will be determined. When PD-L1 CPS is ≥10%, patients will be treated with three cycles nivolumab 240 mg, q3wk, on day 1, 22, 43.
The primary endpoint is feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients.
After surgery, patients attend study visits at day 8 and at day 29. Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events. 90 days postoperative, surgical complications according to the Clavien-dindo classification will be evaluated. Thereafter, patients will be followed according to standard clinical guidelines. Tumor biopsies/material preservation is required at baseline and during surgery.
Main secondary endpoints are:
- To identify pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
- To describe immune-related grade 3/4 and all grade toxicities
- To describe RFS and OS
- Translational: Effects of immunotherapy on the tumor microenvironment based on RNA signatures and changes in immune infiltrates between baseline and resection.
- Conditions
- Urothelial Carcinoma
- Being tested
- Nivolumab
- Medical subject headings
- Carcinoma, Transitional Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
On day 1, 22, and 43 240mg
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab monotherapy | Experimental | Day 1: nivolumab 240 mg Day 22: nivolumab 240 mg Day 43: nivolumab 240 mg Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
Percentage of patients that underwent surgery within 12 weeks after study start will be assessed
Measured: At 12 weeks
Secondary outcomes (5)
Pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
Efficacy of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients, assessed by the percentage of pathological complete response rate after cystectomy according to pathological response criteria
Measured: At 12 weeks
Toxicity of pre-operative nivolumab
All grade toxicities and immune-related toxicity of grade 3-4
Measured: From first inusion untill 100 days after the last infusion with nivolumab
Relapse free survival and overall survival
During follow-up, every 6 months untill 3 years postoperative, relapse free survival will be evaluated. Overall survival will be evaluated by phone calls
Measured: From first infusion untill 3 years postoperative
Monitor peri-surgical complications
Peri-operative complications and morbidity will be graded according to the Clavien-Dindo classification
Measured: From surgery untill 90 days after surgery
Translational: effects of nivolumab on the tumor microenvironment
Resistance mechanisms are explored by comparing immune (cell) infiltrates in responders and nonresponders in pre- and post treatment tissue [Multiplex immunohistochemistry, RNA seq]
Measured: At 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2021
- Study start23 Aug 2021
- Primary completion2 Jun 2023
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by The Netherlands Cancer InstituteThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Multicenter, open-label phase 1b clinical trial
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Netherlands Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- 4SC AG
- Responsible party
- Sponsor
- Investigators
- M.S. van der Heijden, Dr., Principal investigator, The Netherlands Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04871594
- Sponsor's protocol ID
- M21TUR
- Acronym
- TURANDOT
- Status last verified
- Mar 2025
- First submitted
- 29 Apr 2021
- Last updated
- 5 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Trial in Stage II-III Urothelial Cancer to Explore Pre-operative Immunotherapy
- ClinicalTrials.gov ID
- NCT04871594
- Acronym / sponsor ID
- TURANDOT / M21TUR
- Conditions
- Urothelial Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- The Netherlands Cancer InstituteUniversity, hospital or other
- Collaborators
- 4SC AG
- Study start
- 23 Aug 2021 (actual)
- Primary completion
- 2 Jun 2023 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 4 May 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.
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients. This study can be adapted or expanded based on the results obtained.
Detailed description
This is a phase 1b feasibility study of pre-operative immunotherapy in PD-L1 positive resectable stage II-III urothelial cancer patients.
Urothelial cancer patients will be included that are diagnosed with either:
- cT2-4aN0M0 OR
- cT1-4aN1-3M0
PD-L1 status will be determined. When PD-L1 CPS is ≥10%, patients will be treated with three cycles nivolumab 240 mg, q3wk, on day 1, 22, 43.
The primary endpoint is feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients.
After surgery, patients attend study visits at day 8 and at day 29. Their final study visit for physical examination and laboratory testing is at day 57 (+/- 7 days), which is scheduled to anticipate late-onset adverse events. 90 days postoperative, surgical complications according to the Clavien-dindo classification will be evaluated. Thereafter, patients will be followed according to standard clinical guidelines. Tumor biopsies/material preservation is required at baseline and during surgery.
Main secondary endpoints are:
- To identify pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
- To describe immune-related grade 3/4 and all grade toxicities
- To describe RFS and OS
- Translational: Effects of immunotherapy on the tumor microenvironment based on RNA signatures and changes in immune infiltrates between baseline and resection.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Multicenter, open-label phase 1b clinical trial
| Arm | Type | Receives |
|---|---|---|
| Nivolumab monotherapy | Experimental | Drug: NivolumabDay 1: nivolumab 240 mg Day 22: nivolumab 240 mg Day 43: nivolumab 240 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Willing and able to provide informed consent
- Age ≥ 18 years
- Resectable muscle-invasive UC (upper urinary tract allowed), defined as:
- World Health Organization (WHO) performance Status 0 or 1.
- Urothelial cancer is the dominant histology (>70%).
Key exclusion criteria (15 listed)
- Subjects with active autoimmune disease in the past 2 years. Patients with diabetes mellitus, properly controlled hypothyroidism or hyperthyroidism, vitiligo, psoriasis or other mild skin disease can still be included.
- Documented history of severe autoimmune disease (e.g. inflammatory bowel disease, myasthenia gravis).
- Prior CTLA-4 or PD-1/PD-L1-targeting immunotherapy.
- Known history of Human Immunodeficiency Virus infection or tuberculosis, or other active infection requiring therapy at the time of inclusion.
- Positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
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 |
|---|---|---|
| NivolumabAlso: OpdivoOn day 1, 22, and 43 240mg | Drug | Nivolumab monotherapy |
Primary outcome
Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
Time frame: At 12 weeks
Percentage of patients that underwent surgery within 12 weeks after study start will be assessed
5 secondary outcomes
Pathological complete response rates of nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients
Time frame: At 12 weeks
Toxicity of pre-operative nivolumab
Time frame: From first inusion untill 100 days after the last infusion with nivolumab
Relapse free survival and overall survival
Time frame: From first infusion untill 3 years postoperative
Monitor peri-surgical complications
Time frame: From surgery untill 90 days after surgery
Translational: effects of nivolumab on the tumor microenvironment
Time frame: At 12 weeks
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 5 Mar 2025.
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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.
M.S. van der Heijden, Dr. principal investigator
The Netherlands Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab in people with Urothelial Carcinoma, run by The Netherlands Cancer Institute at 2 sites in Netherlands.
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 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 5 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Feasibility of pre-operative nivolumab in PD-L1 positive resectable stage II-III urothelial cancer patients (time frame: At 12 weeks). 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 5 Mar 2025.