NCT05753839

Brief 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. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
69mo left

Started Jul 2023

Longer than P75 for not_applicable

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Jul 2023Dec 2031

First Submitted

Initial submission to the registry

January 17, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

March 3, 2023

Completed
4 months until next milestone

Study Start

First participant enrolled

July 1, 2023

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 27, 2027

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2031

Last Updated

June 22, 2023

Status Verified

June 1, 2023

Enrollment Period

4.5 years

First QC Date

January 17, 2023

Last Update Submit

June 19, 2023

Conditions

Kidney CancerClear Cell Renal Cell Carcinoma MetastaticSynchronous Neoplasm

Outcome Measures

Primary Outcomes (1)

  • 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.

    5 years follow-up

Secondary Outcomes (10)

  • Progression free survival

    5 years follow-up

  • Objective response rate

    5 years follow-up

  • Number of participants with treatment-related adverse events

    5 years follow-up

  • Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications

    5 years follow-up

  • Tumor infiltrating lymphocytes

    5 years follow-up

  • +5 more secondary outcomes

Study Arms (3)

Upfront cytoreductive nephrectomy

EXPERIMENTAL

Cytoreductive nephrectomy±metastasectomy, followed by induction therapy with nivolumab plus ipilimumab combination and maintenance therapy with nivolumab.

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.

Procedure: Cytoreductive nephrectomy±metastasectomy

No surgery

ACTIVE COMPARATOR

Induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab.

Other: Human-derived materials sampling

Interventions

Cytoreductive nephrectomy±metastasectomyPROCEDURE

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.

Also known as: Human-derived materials sampling
Upfront cytoreductive nephrectomy
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.

No surgery

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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.)
  • +3 more criteria

You may not qualify if:

  • 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.
  • No symptomatic brain metastasis requiring systemic corticosteroids (\> 10 mg daily prednisone equivalent)
  • 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.)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Gangnam Severance Hospital

Seoul, South Korea

NOT YET RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, South Korea

RECRUITING

Yongin Severance Hospital

Yongin-si, South Korea

NOT YET RECRUITING

Related Publications (1)

  • Park 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.

    PMID: 38961439DERIVED

MeSH Terms

Conditions

Kidney NeoplasmsClear-cell metastatic renal cell carcinomaNeoplasms, Multiple Primary

Condition Hierarchy (Ancestors)

Urologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Study Officials

  • Won Sik Ham

    Department of Urology and Urological Science Institute, Yonsei University College of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Won Sik Ham

CONTACT

02-2228-2310uroham@yuhs.ac

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 17, 2023

First Posted

March 3, 2023

Study Start

July 1, 2023

Primary Completion (Estimated)

December 27, 2027

Study Completion (Estimated)

December 31, 2031

Last Updated

June 22, 2023

Record last verified: 2023-06

Data Sharing

IPD Sharing
Will not share

Locations

KR(3)