Clinical trial NCT05753839: The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
Official title: The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Kidney Cancer
Clear Cell Renal Cell Carcinoma Metastatic
Synchronous Neoplasm
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2023-03-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.)

Primary outcomes:
measure: Overall survival
timeFrame: 5 years follow-up
Secondary outcomes:
measure: Progression free survival
timeFrame: 5 years follow-up
measure: Objective response rate
timeFrame: 5 years follow-up
measure: Number of participants with treatment-related adverse events
timeFrame: 5 years follow-up
measure: Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications
timeFrame: 5 years follow-up
measure: Tumor infiltrating lymphocytes
timeFrame: 5 years follow-up
measure: Genetic mutation profiles of primary tissue
timeFrame: 5 years follow-up
measure: Genetic mutation profile of circulating tumor DNA
timeFrame: 5 years follow-up
measure: Genetic mutation profile or urine tumor DNA
timeFrame: 5 years follow-up
measure: Profile of gut microbiome
timeFrame: 5 years follow-up
measure: Profile of urine microbiome
timeFrame: 5 years follow-up
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
city: Yongin-si
country: Korea, Republic of
facility: Yongin Severance Hospital
Study officials:
affiliation: Department of Urology and Urological Science Institute, Yonsei University College of Medicine
name: Won Sik Ham
role: PRINCIPAL_INVESTIGATOR
References: