Trial Title:
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
NCT ID:
NCT05753839
Condition:
Kidney Cancer
Clear Cell Renal Cell Carcinoma Metastatic
Synchronous Neoplasm
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Neoplasms, Multiple Primary
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Cytoreductive nephrectomy±metastasectomy
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.
Arm group label:
Upfront cytoreductive nephrectomy
Other name:
Human-derived materials sampling
Intervention type:
Procedure
Intervention name:
Cytoreductive nephrectomy±metastasectomy
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.
Arm group label:
Deferred cytoreductive nephrectomy
Other name:
Human-derived materials sampling
Intervention type:
Other
Intervention name:
Human-derived materials sampling
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.
Arm group label:
No surgery
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Core needle biopsy proven metastatic renal cell carcinoma - clear cell histologic
subtypes only acceptable.
2. Synchronous metastatic renal cell carcinoma with the primary tumor present in the
kidney.
3. Patient must be willing to provide their human-derived materials.
4. Age ≥19.
5. Signed written informed consent obtained prior to any study specific procedures.
6. Patient must be willing and able to comply with the protocol.
7. Measurable disease as per RECIST v 1.1
8. Life expectancy of greater than 4 months.
9. Patients with more than one prognostic factor by the International Metastatic RCC
Database Consortium (IMDC) criteria (intermediate- or poor-risk group).
10. 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.
11. Karnofsky Performance status ≥70
12. Females with a negative serum pregnancy test unless childbearing potential can be
otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating.
13. 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).
14. 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:
1. Prior systemic treatment for mRCC
2. Major surgical procedure, open surgical biopsy, or significant traumatic injury
within 28 days prior to enrollment
3. Other cancer within 5 years.
4. 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.
5. No symptomatic brain metastasis requiring systemic corticosteroids (> 10 mg daily
prednisone equivalent)
6. Recent (within the 30 days prior to inclusion) treatment with another
investigational drug or participation in another investigational study.
7. 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.
8. Oral or i.v. antibiotics administered 14 days prior to initiation of systemic
therapy.
9. Any positive test for hepatitis B- or C-Virus indicating acute or chronic infection.
10. Known hypersensitivity to monoclonal antibodies.
11. Known history of testing positive for human immunodeficiency virus (HIV) or known
acquired immunodeficiency syndrome (AIDS).
12. Patients disagreeing to provide their human-derived materials.
13. Patients not willing and able to comply with the protocol.
14. Vulnerable subjects (such as children, prisoners, pregnant women, mentally disabled
persons, or economically or educationally disadvantaged persons).
15. Patients who cannot read and understand the consent form. (illiterate, foreigners,
etc.)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Gangnam Severance Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Kang Su Cho
Phone:
82-2-2019-3470
Email:
kscho99@yuhs.ac
Facility:
Name:
Yonsei University Health System, Severance Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Won Sik Ham
Phone:
02-2228-2310
Email:
uroham@yuhs.ac
Facility:
Name:
Yongin Severance Hospital
Address:
City:
Yongin-si
Country:
Korea, Republic of
Status:
Not yet recruiting
Contact:
Last name:
Jongchan Kim
Phone:
82-10-9364-2395
Email:
lumpakcef@yuhs.ac
Start date:
July 2023
Completion date:
December 31, 2031
Lead sponsor:
Agency:
Yonsei University
Agency class:
Other
Source:
Yonsei University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05753839
