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

Prior treatment

• Prior systemic treatment for mRCC
• Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to enrollment
• 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.
• Oral or i.v. antibiotics administered 14 days prior to initiation of systemic therapy.

Other illness

• Other cancer within 5 years.
• 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.
• 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).

Other

• 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.)

• 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)