Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-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 3 years (except in situ basal cell carcinoma and localised prostate cancer with undetectable PSA).
• 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.
• Known hypersensitivity to monoclonal antibodies.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Any positive test for hepatitis B- or C-Virus indicating acute or chronic infection.

• Signed written informed consent obtained prior to any study specific procedures.
• Patient must be willing and able to comply with the protocol.
• Age ≥18.
• Core needle biopsy proven metastatic renal cell carcinoma - all histologic subtypes acceptable.
• Synchronous metastatic renal cell carcinoma with the primary tumor present in the kidney.
• Measurable disease as per RECIST v 1.1
• Patients for which Nivolumab/Ipilimumab or a TKI/IO-combination is considered indicated according to the recommendations by the European Medicines Agency and the national health authorities of participating countries. The prescription of nivolumab/ipilimumab or a TKI/IO-combination in the circumstances of the study is considered as a standard treatment.
• 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).
• Karnofsky Performance status ≥70
• Life expectancy of greater than 4 months.
• The required laboratory values are as follows:
  • Adequate bone marrow function (Leucocytes \> 3.0 x 109/l, platelets \> 100 x 109/l, hemoglobin \> 6.0 mmol/l or \> 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 or ≤ 5 x ULN if liver lesions)
  • Adequate kidney function (eGFR \> 35 mL/min)