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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
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.
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.
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.
Gangnam Severance Hospital
Seoul, South Korea
NOT_YET_RECRUITINGYonsei University Health System, Severance Hospital
Seoul, South Korea
RECRUITINGYongin Severance Hospital
Yongin-si, South Korea
NOT_YET_RECRUITINGOverall survival
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
Progression free survival
According to the RECIST v1.1
Time frame: 5 years follow-up
Objective response rate
According to the RECIST v1.1
Time frame: 5 years follow-up
Number of participants with treatment-related adverse events
By Common Terminology Criteria for Adverse Events version 5.0
Time frame: 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
Time frame: 5 years follow-up
Tumor infiltrating lymphocytes
Measured by flowcytometry at baseline and after surgery and/or after ICIs compared with OS, PFS, ORR
Time frame: 5 years follow-up
Genetic mutation profiles of primary tissue
Measured by Next generation sequencing (NGS) methods compared with OS, PFS, and ORR
Time frame: 5 years follow-up
Genetic mutation profile of circulating tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Time frame: 5 years follow-up
Genetic mutation profile or urine tumor DNA
Measured by NGS methods compared with OS, PFS, and ORR
Time frame: 5 years follow-up
Profile of gut microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Time frame: 5 years follow-up
Profile of urine microbiome
Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR
Time frame: 5 years follow-up
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