Kidney CancerSEVURO-CNNCT05753839
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
A study testing Cytoreductive nephrectomy±metastasectomy and Human-derived materials sampling in people with Kidney Cancer and Clear Cell Renal Cell Carcinoma Metastatic, run by Yonsei University at 3 sites in South Korea.
Trial summary
BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been questioned and remains undetermined in the immuno-oncology era. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer, Clear Cell Renal Cell Carcinoma Metastatic, Synchronous Neoplasm
- What is being tested?
- Cytoreductive nephrectomy±metastasectomy and Human-derived materials sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesSouth Korea
- Study dates
- Jul 2023to 31 Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Core needle biopsy proven metastatic renal cell carcinoma - clear cell histologic subtypes only acceptable.
- Synchronous metastatic renal cell carcinoma with the primary tumor present in the kidney.
- Patient must be willing to provide their human-derived materials.
- Age ≥19.
- Signed written informed consent obtained prior to any study specific procedures.
- Patient must be willing and able to comply with the protocol.
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- Measurable disease as per RECIST v 1.1
- Life expectancy of greater than 4 months.
- Patients with more than one prognostic factor by the International Metastatic RCC Database Consortium (IMDC) criteria (intermediate- or poor-risk group).
- Patients for which Nivolumab/Ipilimumab considered indicated according to the recommendations by the national health authorities. The prescription of nivolumab/ipilimumab in the circumstances of the study is considered as a standard treatment.
- Karnofsky Performance status ≥70
- Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating.
- Fertile women of childbearing potential (<2 years after last menstruation) and men must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgical sterilization).
- The required laboratory values are as follows:
- Adequate bone marrow function (Absolute neutrophil count > 1500/mm3, platelets > 100 x 103/µl, hemoglobin > 10.0 g/dL.)
- International normalized ratio (INR) ≤ 1.2 x upper limit of normal (ULN)
- Adequate hepatic function (bilirubin ≤ 1.5 x ULN, ALAT ≤ 2.5 x ULN)
- Adequate kidney function (eGFR > 35 mL/min)
Who cannot join
- Prior systemic treatment for mRCC
- Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to enrollment
- Other cancer within 5 years.
- Clinically significant (i.e active) cardiovascular disease for example cerebrovascular accidents (< 6 months before inclusion), myocardial infarction (< 6 months before inclusion), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure.
- No symptomatic brain metastasis requiring systemic corticosteroids (> 10 mg daily prednisone equivalent)
- Recent (within the 30 days prior to inclusion) treatment with another investigational drug or participation in another investigational study.
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- Any active or recent history of a known or suspected autoimmune disease or recent history of a condition that require systemic corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications, excluding inhaled steroids and topical steroids. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, psoriasis not requiring systemic treatment are permitted to enroll.
- Oral or i.v. antibiotics administered 14 days prior to initiation of systemic therapy.
- Any positive test for hepatitis B- or C-Virus indicating acute or chronic infection.
- Known hypersensitivity to monoclonal antibodies.
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
- Patients disagreeing to provide their human-derived materials.
- Patients not willing and able to comply with the protocol.
- Vulnerable subjects (such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons).
- Patients who cannot read and understand the consent form. (illiterate, foreigners, etc.)
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea3 sites, 3 recruiting
- Not yet recruiting
Gangnam Severance Hospital
Seoul
Kang Su Cho, 82-2-2019-3470, kscho99@yuhs.ac
- Recruiting
Yonsei University Health System, Severance Hospital
Seoul
Won Sik Ham, 02-2228-2310, uroham@yuhs.ac
- Not yet recruiting
Yongin Severance Hospital
Yongin-si
Jongchan Kim, 82-10-9364-2395, lumpakcef@yuhs.ac
About this study
BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been questioned and remains undetermined in the immuno-oncology era. Results from the two randomized trials, CARMENA and SURTIME, have questioned the role and timing of the surgery in these patients, however, these trials have only used the targeted therapy, sunitinib. With the advent of more effective systemic therapies including immune checkpoint inhibitors (ICIs), the role of surgical therapy should be reexamined.
RATIONALE: The therapeutic effects of ICIs have demonstrated improved oncological outcomes compared to sunitinib. The updated results reported the beneficial role of upfront and deferred CN approach for selected patients. No studies have formally investigated the role of CN in the immune-oncology era where combinatorial use of CN plus ICIs might be beneficial.
Read more
HYPOTHESIS: Upfront or deferred CN will improve oncological outcomes (overall survival, and progression free survival) in patients with synchronous mRCC and ≤3 IMDC risk features compared to immune checkpoint inhibitors (nivolumab plus ipilimumab combination) alone.
This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of the potential role of CN in combination with immunotherapy in mRCC patients with IMDC intermediate and poor risk.
- Being tested
- Cytoreductive nephrectomy±metastasectomy, Human-derived materials sampling
- Medical subject headings
- Kidney Neoplasms, Clear-cell metastatic renal cell carcinoma, Neoplasms, Multiple Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytoreductive nephrectomy±metastasectomyProcedure or surgery
Also called Human-derived materials sampling
Partial or complete nephrectomy by open, laparoscopic, or robotic approach and/or metastasectomy Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, surgery, after induction therapy, and after 3 months of maintenance therapy.
Cytoreductive nephrectomy±metastasectomyProcedure or surgery
Also called Human-derived materials sampling
Partial or complete nephrectomy by open, laparoscopic, or robotic approach and/or metastasectomy Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, surgery, after induction therapy, and after 3 months of maintenance therapy.
Human-derived materials samplingOther
Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, after induction therapy, and after 3 months of maintenance therapy.
| Study group | Role | What they receive |
|---|---|---|
| Upfront cytoreductive nephrectomy | Experimental | Cytoreductive nephrectomy±metastasectomy, followed by induction therapy with nivolumab plus ipilimumab combination and maintenance therapy with nivolumab. Receives: Procedure: Cytoreductive nephrectomy±metastasectomy |
| Deferred cytoreductive nephrectomy | Experimental | Cytoreductive nephrectomy±metastasectomy after induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab. Receives: Procedure: Cytoreductive nephrectomy±metastasectomy |
| No surgery | Active comparator | Induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab. Receives: Other: Human-derived materials sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.
Measured: 5 years follow-up
Secondary outcomes (10)
Progression free survival
According to the RECIST v1.1
Measured: 5 years follow-up
Objective response rate
According to the RECIST v1.1
Measured: 5 years follow-up
Number of participants with treatment-related adverse events
By Common Terminology Criteria for Adverse Events version 5.0
Measured: 5 years follow-up
Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications
Assessed according to the Clavien-Dindo classification of surgical complications
Measured: 5 years follow-up
Tumor infiltrating lymphocytes
Measured by flowcytometry at baseline and after surgery and/or after ICIs compared with OS, PFS, ORR
Measured: 5 years follow-up
Genetic mutation profiles of primary tissue
Measured by Next generation sequencing (NGS) methods compared with OS, PFS, and ORR
Measured: 5 years follow-up
Genetic mutation profile of circulating tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Measured: 5 years follow-up
Genetic mutation profile or urine tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Measured: 5 years follow-up
Profile of gut microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Measured: 5 years follow-up
Profile of urine microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Measured: 5 years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2023
- Study startJul 2023 (estimated)
- Primary completion27 Dec 2027 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Won Sik Ham, Principal investigator, Department of Urology and Urological Science Institute, Yonsei University College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05753839
- Sponsor's protocol ID
- 4-2022-1453
- Acronym
- SEVURO-CN
- Status last verified
- Jun 2023
- First submitted
- 17 Jan 2023
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Flammia RS, Campi R, Bologna E, Bertolo R, Leonardo C, Calabro F, Amparore D, Simone G; Young Academic Urologists (YAU) Renal Cancer Working Group. Cytoreductive nephrectomy in the era of immune-checkpoint inhibitors: back to the future? BJU Int. 2026 May;137(5):763-769. doi: 10.1111/bju.70168. Epub 2026 Feb 11.
PubMed 41673778Park JS, Kim J, Jeon J, Lee J, Jang WS, Lee SH, Han WK, Choi YD, Koo KC, Cho KS, Chung BH, Ham WS. The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial. Trials. 2024 Jul 3;25(1):447. doi: 10.1186/s13063-024-08234-2.
PubMed 38961439
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
- ClinicalTrials.gov ID
- NCT05753839
- Acronym / sponsor ID
- SEVURO-CN / 4-2022-1453
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Jul 2023 (estimated)
- Primary completion
- 27 Dec 2027 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 3 Mar 2023 (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.
BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been questioned and remains undetermined in the immuno-oncology era. Results from the two randomized trials, CARMENA and SURTIME, have questioned the role and timing of the surgery in these patients, however, these trials have only used the targeted therapy, sunitinib. With the advent of more effective systemic therapies including immune checkpoint inhibitors (ICIs), the role of surgical therapy should be reexamined.
RATIONALE: The therapeutic effects of ICIs have demonstrated improved oncological outcomes compared to sunitinib. The updated results reported the beneficial role of upfront and deferred CN approach for selected patients. No studies have formally investigated the role of CN in the immune-oncology era where combinatorial use of CN plus ICIs might be beneficial.
HYPOTHESIS: Upfront or deferred CN will improve oncological outcomes (overall survival, and progression free survival) in patients with synchronous mRCC and ≤3 IMDC risk features compared to immune checkpoint inhibitors (nivolumab plus ipilimumab combination) alone.
This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of the potential role of CN in combination with immunotherapy in mRCC patients with IMDC intermediate and poor risk.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Upfront cytoreductive nephrectomy | Experimental | Procedure: Cytoreductive nephrectomy±metastasectomyCytoreductive nephrectomy±metastasectomy, followed by induction therapy with nivolumab plus ipilimumab combination and maintenance therapy with nivolumab. |
| Deferred cytoreductive nephrectomy | Experimental | Procedure: Cytoreductive nephrectomy±metastasectomyCytoreductive nephrectomy±metastasectomy after induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab. |
| No surgery | Active comparator | Other: Human-derived materials samplingInduction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Core needle biopsy proven metastatic renal cell carcinoma - clear cell histologic subtypes only acceptable.
- Synchronous metastatic renal cell carcinoma with the primary tumor present in the kidney.
- Patient must be willing to provide their human-derived materials.
- Age ≥19.
- Signed written informed consent obtained prior to any study specific procedures.
Key exclusion criteria (15 listed)
- Prior systemic treatment for mRCC
- Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to enrollment
- Other cancer within 5 years.
- Clinically significant (i.e active) cardiovascular disease for example cerebrovascular accidents (< 6 months before inclusion), myocardial infarction (< 6 months before inclusion), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure.
- No symptomatic brain metastasis requiring systemic corticosteroids (> 10 mg daily prednisone equivalent)
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 |
|---|---|---|
| Cytoreductive nephrectomy±metastasectomyAlso: Human-derived materials samplingPartial or complete nephrectomy by open, laparoscopic, or robotic approach and/or metastasectomy Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, surgery, after induction therapy, and after 3 months of maintenance therapy. | Procedure or surgery | Upfront cytoreductive nephrectomy |
| Cytoreductive nephrectomy±metastasectomyAlso: Human-derived materials samplingPartial or complete nephrectomy by open, laparoscopic, or robotic approach and/or metastasectomy Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, surgery, after induction therapy, and after 3 months of maintenance therapy. | Procedure or surgery | Deferred cytoreductive nephrectomy |
| Human-derived materials samplingTumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, after induction therapy, and after 3 months of maintenance therapy. | Other | No surgery |
Primary outcome
Overall survival
Time frame: 5 years follow-up
Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.
10 secondary outcomes
Progression free survival
Time frame: 5 years follow-up
Objective response rate
Time frame: 5 years follow-up
Number of participants with treatment-related adverse events
Time frame: 5 years follow-up
Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications
Time frame: 5 years follow-up
Tumor infiltrating lymphocytes
Time frame: 5 years follow-up
Genetic mutation profiles of primary tissue
Time frame: 5 years follow-up
Genetic mutation profile of circulating tumor DNA
Time frame: 5 years follow-up
Genetic mutation profile or urine tumor DNA
Time frame: 5 years follow-up
Profile of gut microbiome
Time frame: 5 years follow-up
Profile of urine microbiome
Time frame: 5 years follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Derived from this study: PubMed 41673778Flammia RS, Campi R, Bologna E, Bertolo R, Leonardo C, Calabro F, Amparore D, Simone G; Young Academic Urologists (YAU) Renal Cancer Working Group. Cytoreductive nephrectomy in the era of immune-checkpoint inhibitors: back to the future? BJU Int. 2026 May;137(5):763-769. doi: 10.1111/bju.70168. Epub 2026 Feb 11.
- Derived from this study: PubMed 38961439Park JS, Kim J, Jeon J, Lee J, Jang WS, Lee SH, Han WK, Choi YD, Koo KC, Cho KS, Chung BH, Ham WS. The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial. Trials. 2024 Jul 3;25(1):447. doi: 10.1186/s13063-024-08234-2.
- 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.
Won Sik Ham principal investigator
Department of Urology and Urological Science Institute, Yonsei University College of Medicine
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cytoreductive nephrectomy±metastasectomy and Human-derived materials sampling in people with Kidney Cancer and Clear Cell Renal Cell Carcinoma Metastatic, run by Yonsei University at 3 sites in South Korea.
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 18 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: looking for participants now, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Won Sik Ham (02-2228-2310, uroham@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 5 years follow-up). 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 NCT05753839, which also lists 2 linked publications.
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 22 Jun 2023.