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The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial (SEVURO-CN)

Primary Purpose

Kidney Cancer, Clear Cell Renal Cell Carcinoma Metastatic, Synchronous Neoplasm

Status
Recruiting
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Cytoreductive nephrectomy±metastasectomy
Cytoreductive nephrectomy±metastasectomy
Human-derived materials sampling
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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.) 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) Exclusion Criteria: 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. 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.)

Sites / Locations

  • Gangnam Severance Hospital
  • Yonsei University Health System, Severance HospitalRecruiting
  • Yongin Severance Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Upfront cytoreductive nephrectomy

Deferred cytoreductive nephrectomy

No surgery

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progression free survival
According to the RECIST v1.1
Objective response rate
According to the RECIST v1.1
Number of participants with treatment-related adverse events
By Common Terminology Criteria for Adverse Events version 5.0
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
Tumor infiltrating lymphocytes
Measured by flowcytometry at baseline and after surgery and/or after ICIs compared with OS, PFS, ORR
Genetic mutation profiles of primary tissue
Measured by Next generation sequencing (NGS) methods compared with OS, PFS, and ORR
Genetic mutation profile of circulating tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Genetic mutation profile or urine tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Profile of gut microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Profile of urine microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR

Full Information

First Posted
January 17, 2023
Last Updated
June 19, 2023
Sponsor
Yonsei University
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1. Study Identification

Unique Protocol Identification Number
NCT05753839
Brief Title
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
Acronym
SEVURO-CN
Official Title
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 2023 (Anticipated)
Primary Completion Date
December 27, 2027 (Anticipated)
Study Completion Date
December 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer, Clear Cell Renal Cell Carcinoma Metastatic, Synchronous Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Upfront cytoreductive nephrectomy
Arm Type
Experimental
Arm Description
Cytoreductive nephrectomy±metastasectomy, followed by induction therapy with nivolumab plus ipilimumab combination and maintenance therapy with nivolumab.
Arm Title
Deferred cytoreductive nephrectomy
Arm Type
Experimental
Arm Description
Cytoreductive nephrectomy±metastasectomy after induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab.
Arm Title
No surgery
Arm Type
Active Comparator
Arm Description
Induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab.
Intervention Type
Procedure
Intervention Name(s)
Cytoreductive nephrectomy±metastasectomy
Other Intervention Name(s)
Human-derived materials sampling
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Cytoreductive nephrectomy±metastasectomy
Other Intervention Name(s)
Human-derived materials sampling
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Human-derived materials sampling
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall survival
Description
Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.
Time Frame
5 years follow-up
Secondary Outcome Measure Information:
Title
Progression free survival
Description
According to the RECIST v1.1
Time Frame
5 years follow-up
Title
Objective response rate
Description
According to the RECIST v1.1
Time Frame
5 years follow-up
Title
Number of participants with treatment-related adverse events
Description
By Common Terminology Criteria for Adverse Events version 5.0
Time Frame
5 years follow-up
Title
Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications
Description
Assessed according to the Clavien-Dindo classification of surgical complications
Time Frame
5 years follow-up
Title
Tumor infiltrating lymphocytes
Description
Measured by flowcytometry at baseline and after surgery and/or after ICIs compared with OS, PFS, ORR
Time Frame
5 years follow-up
Title
Genetic mutation profiles of primary tissue
Description
Measured by Next generation sequencing (NGS) methods compared with OS, PFS, and ORR
Time Frame
5 years follow-up
Title
Genetic mutation profile of circulating tumor DNA
Description
Measured by NGS methods compared with OS, PFS, and ORR
Time Frame
5 years follow-up
Title
Genetic mutation profile or urine tumor DNA
Description
Measured by NGS methods compared with OS, PFS, and ORR
Time Frame
5 years follow-up
Title
Profile of gut microbiome
Description
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Time Frame
5 years follow-up
Title
Profile of urine microbiome
Description
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Time Frame
5 years follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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.) 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) Exclusion Criteria: 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. 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.)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Won Sik Ham
Phone
02-2228-2310
Email
uroham@yuhs.ac
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Won Sik Ham
Organizational Affiliation
Department of Urology and Urological Science Institute, Yonsei University College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gangnam Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kang Su Cho
Phone
82-2-2019-3470
Email
kscho99@yuhs.ac
Facility Name
Yonsei University Health System, Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Won Sik Ham
Phone
02-2228-2310
Email
uroham@yuhs.ac
Facility Name
Yongin Severance Hospital
City
Yongin-si
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jongchan Kim
Phone
82-10-9364-2395
Email
lumpakcef@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD
No

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The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial

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