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Uppskjuten cytoreduktiv nefrektomi vid synkront metastaserande njurcellscancer: The NORDIC-SUN-Trial (NORDIC-SUN)

22 september 2026 uppdaterad av: Niels Fristrup

Multicenter randomiserad prövning av uppskjuten cytoreduktiv nefrektomi vid synkront metastaserande njurcellscancer som tar emot checkpoint-hämmare: en DaRenCa- och NoRenCa-prövning som utvärderar effekten av kirurgi eller ingen kirurgi. NORDISK-SOL-försöket

BACKGROUND: For synchronous metastatic renal cell carcinoma (RCC), surgical resection of the primary tumor in the presence of distant metastases has been the standard of therapy for select patients followed by systemic therapy. In the era of TKIs two randomized trials, CARMENA and SURTIME, have questioned the role and timing of surgery in these patients, results point towards no surgery or a deferred approach.

RATIONALE: The antitumor activity of immune checkpoint blockage (ICB) is more potent than other therapy in mRCC. The deferred cytoreductive nephrectomy approach ensures systemic therapy for all patients, avoid systemic treatment delay, and spare surgery in patients with progressive tumors. Current data only point towards a survival benefit for cytoreductive nephrectomy in intermediate risk patients, but not in poor risk patients

HYPOTHESIS: Deferred cytoreductive nephrectomy after initial nivolumab combined with ipilimumab or a TKI/IO-combination will improve OS in patients with synchronous metastatic RCC and ≤3 IMDC risk features

This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of deferred cytoreductive nephrectomy compared with no surgery following initial nivolumab combined with ipilimumab or a TKI-combination, in mRCC patients with IMDC intermediate and poor risk.

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Detaljerad beskrivning

OUTLINE: This is a multicenter trial, patients are stratified according to institution, treatment choice, number of IMDC risk factors, and combined elevated neutrophil-lymphocyte ratio and hyponatremia.

All patients will receive induction checkpoint immunotherapy immediately after inclusion. After 3 months or a total of 4 series of nivolumab combined with ipilimumab or a TKI/IO-combination, the patient will be discussed for resectability at the multidisciplinary meeting (MDT). Whether the patient is eligible for cytoreductive nephrectomy is at the discretion of the urologist at the local MDT. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy will then undergo randomization. Patients deemed not suitable for surgery or have > 3 IMDC risk features at the 3 month evaluation continue systemic therapy for 3 months, followed by a 2nd evaluation. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy at 2nd evaluation will then undergo randomization. Patients deemed not suitable for surgery or have > 3 IMDC risk features at the 6 month evaluation continue systemic therapy. Nivolumab may continue until unacceptable toxicity or total treatment length of 2 years from inclusion.

ARM A: Deferred cytoreductive nephrectomy, followed by maintenance nivolumab or a TKI/IO-combination.

ARM B: No surgery, receive maintenance nivolumab or a TKI/IO-combination.

Patients undergo tumor tissue, blood, and stool collection at baseline, 3 and 6 months, for planned translational research.

Studietyp

Interventionell

Inskrivning (Beräknad)

400

Fas

  • Inte tillämpbar

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

  • Danmark
  • Finland
      • Helsinki, Finland
        • Rekrytering
        • Clinical Trial Unit, Helsinki University Central Hospital
        • Huvudutredare:
          • Katriina Jalkanen, MD, PhD
        • Kontakt:
  • Norge
      • Bergen, Norge
      • Kristiansand, Norge, 4615
        • Rekrytering
        • Centre for Cancer Treatment, Sørlandet Hospital Trust, Kristiansand
        • Kontakt:
        • Huvudutredare:
          • Anne Helene Køstner, MD, PhD
      • Stavanger, Norge
        • Rekrytering
        • Department of Oncology, Stavanger Universitetssykehus
        • Kontakt:
        • Huvudutredare:
          • Maria N Vigmostad, MD
      • Trondheim, Norge, 7030
        • Rekrytering
        • Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital
        • Kontakt:
        • Huvudutredare:
          • Martine Hansen Gaarder, MD
      • Ålesund, Norge
        • Rekrytering
        • Department of Oncology, Ålesund Universitetsykehus
        • Kontakt:
        • Huvudutredare:
          • Bjørg Y Aksnessæther, MD
    • Vestfold
      • Tønsberg, Vestfold, Norge, 3103
        • Rekrytering
        • Center for Cancer and Blood Diseases, Vestfold Hospital Trust
        • Kontakt:
          • Marius Ioan-Taran, MD
          • Telefonnummer: 0047-33342000
          • E-post: matara@siv.no
        • Huvudutredare:
          • Marius Ioan-Taran, MD
  • Sverige
      • Stockholm, Sverige, SSE-17177

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Signed written informed consent obtained prior to any study specific procedures.

  2. Patient must be willing and able to comply with the protocol.

  3. Age ≥18.

  4. Core needle biopsy proven metastatic renal cell carcinoma - all histologic subtypes acceptable.

  5. Synchronous metastatic renal cell carcinoma with the primary tumor present in the kidney.

  6. Measurable disease as per RECIST v 1.1

  7. 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.

  8. Females with a negative serum pregnancy test unless childbearing potential can be otherwise excluded (postmenopausal, hysterectomy or oophorectomy) and not lactating.

  9. 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).

  10. Karnofsky Performance status ≥70

  11. Life expectancy of greater than 4 months.

  12. 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)

Exclusion Criteria:

  1. Prior systemic treatment for mRCC
  2. Other cancer within 3 years (except in situ basal cell carcinoma and localised prostate cancer with undetectable PSA).
  3. Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to enrollment
  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. Known hypersensitivity to monoclonal antibodies.
  9. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  10. Any positive test for hepatitis B- or C-Virus indicating acute or chronic infection.
  11. Oral or i.v. antibiotics administered 14 days prior to initiation of systemic therapy.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Deferred nephrectomy

Surgery after induction therapy with IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.
Procedur: Cytoreductive nephrectomy

Partial or complete nephrectomy by open, laparoscopic, or robotic approach.

Övrig: Tissue sampling

Tumor biopsies, blood, and stool specimens for translational biomarker research will be sampled at baseline and after 3 or 6 months.
Aktiv komparator: No surgery

Induction therapy wih IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.
Övrig: Tissue sampling

Tumor biopsies, blood, and stool specimens for translational biomarker research will be sampled at baseline and after 3 or 6 months.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Overall survival
Tidsram: Minimum 3 years follow-up

Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.
Minimum 3 years follow-up

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Progression free survival
Tidsram: 3 years follow-up

According to the RECIST v1.1
3 years follow-up
Time to subsequent systemic therapy
Tidsram: 3 years follow-up

Calculated from date of inclusion to date of initiation of subsequent therapy or death of any cause or censored at the date of last follow-up
3 years follow-up
Objective response rate
Tidsram: 3 years follow-up

According to the RECIST v1.1
3 years follow-up
Rate of patients meeting randomization criteria
Tidsram: 3 or 6 months

Compared with baseline values
3 or 6 months
Fractional percentage of tumor volume (ratio of primary tumor measurement to total sum of target lesions) to survival outcome in deferred cytoreductive nephrectomy patients and no surgery patients
Tidsram: 3 years follow-up

Compared with baseline values
3 years follow-up
Number of participants with treatment-related adverse events as by Common Terminology Criteria for Adverse Events version 5.0.
Tidsram: 3 years follow-up

Evaluation of adverse events
3 years follow-up
Number of participant with surgical morbidity assessed according to the Clavien-Dindo classification of surgical complications
Tidsram: 3 years follow-up

Evaluation of surgical morbidity
3 years follow-up
Tumor infiltrating lymphocytes baseline and after surgery compared with OS, PFS, TST, ORR
Tidsram: 3 year follow-up

As part of a biomarker analysis
3 year follow-up
Immune subsets in blood measured by flowcytometry in serial samples compared with OS, PFS, TST, ORR.
Tidsram: 3 year follow-up

As part of a biomarker analysis
3 year follow-up
Genetic profile of circulation tumor DNA measured by Next generation sequencing (NGS), compared with OS, PFS, TST, ORR.
Tidsram: 3 year follow-up

As part of a biomarker analysis
3 year follow-up
Genetic profile of primary tumor tissue measured by measured by NGS compared with OS, PFS, TST, ORR.
Tidsram: 3 year follow-up

As part of a biomarker analysis
3 year follow-up
Profile of gut microbiome measured by NGS compared OS, PFS, TST, ORR.
Tidsram: 3 year follow-up

As part of a biomarker analysis
3 year follow-up

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Niels Fristrup

Samarbetspartners

Aarhus University Hospital

Utredare

  • Huvudutredare: Niels Fristrup, MD PhD, Department of Oncology, Aarhus University Hospital.

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

6 juli 2020

Primärt slutförande (Beräknad)

1 december 2028

Avslutad studie (Beräknad)

1 december 2031

Studieregistreringsdatum

Först inskickad

3 juni 2019

Först inskickad som uppfyllde QC-kriterierna

4 juni 2019

Första postat (Faktisk)

6 juni 2019

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

23 september 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

22 september 2026

Senast verifierad

1 september 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • NORDIC-SUN

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-delning som stöder informationstyp

  • STUDY_PROTOCOL
  • CSR

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

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