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Utsatt cytoreduktiv nefrektomi ved synkront metastatisk nyrecellekarsinom: The NORDIC-SUN-Trial (NORDIC-SUN)

22. september 2026 oppdatert av: Niels Fristrup

Multisenter randomisert utprøving av utsatt cytoreduktiv nefrektomi i synkront metastatisk nyrecellekarsinom som mottar sjekkpunkthemmere: en DaRenCa- og NoRenCa-forsøk som evaluerer virkningen av kirurgi eller ingen kirurgi. NORDISK-SOL-Trialet

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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

400

Fase

  • Ikke aktuelt

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Danmark
    • Central Region of Denmark
      • Aarhus, Central Region of Denmark, Danmark, 8200
        • Rekruttering
        • Department of Oncology, Aarhus University Hospital
        • Ta kontakt med:
  • Finland
      • Helsinki, Finland
        • Rekruttering
        • Clinical Trial Unit, Helsinki University Central Hospital
        • Hovedetterforsker:
          • Katriina Jalkanen, MD, PhD
        • Ta kontakt med:
  • Norge
      • Bergen, Norge
        • Rekruttering
        • Department of Urology, Haukeland University Hospital
        • Ta kontakt med:
        • Underetterforsker:
          • Karin Hjelle, MD
        • Ta kontakt med:
        • Hovedetterforsker:
          • Christian Beisland, Professor
      • Kristiansand, Norge, 4615
        • Rekruttering
        • Centre for Cancer Treatment, Sørlandet Hospital Trust, Kristiansand
        • Ta kontakt med:
        • Hovedetterforsker:
          • Anne Helene Køstner, MD, PhD
      • Stavanger, Norge
        • Rekruttering
        • Department of Oncology, Stavanger Universitetssykehus
        • Ta kontakt med:
        • Hovedetterforsker:
          • Maria N Vigmostad, MD
      • Trondheim, Norge, 7030
        • Rekruttering
        • Cancer Clinic, St. Olavs Hospital, Trondheim University Hospital
        • Ta kontakt med:
        • Hovedetterforsker:
          • Martine Hansen Gaarder, MD
      • Ålesund, Norge
        • Rekruttering
        • Department of Oncology, Ålesund Universitetsykehus
        • Ta kontakt med:
        • Hovedetterforsker:
          • Bjørg Y Aksnessæther, MD
    • Vestfold
      • Tønsberg, Vestfold, Norge, 3103
        • Rekruttering
        • Center for Cancer and Blood Diseases, Vestfold Hospital Trust
        • Ta kontakt med:
          • Marius Ioan-Taran, MD
          • Telefonnummer: 0047-33342000
          • E-post: matara@siv.no
        • Hovedetterforsker:
          • Marius Ioan-Taran, MD
  • Sverige
      • Stockholm, Sverige, SSE-17177
        • Rekruttering
        • Department of Oncology, Karolinska University Hospital
        • Ta kontakt med:
        • Ta kontakt med:
        • Hovedetterforsker:
          • Magnus Lindskog, MD, PhD
        • Underetterforsker:
          • Per-Olof Lundgren, MD, PhD
        • Underetterforsker:
          • Anders Kjellman, MD, PhD

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Fremgangsmåte: Cytoreductive nephrectomy

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

Annen: 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.
Annen: Tissue sampling

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

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Overall survival
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Progression free survival
Tidsramme: 3 years follow-up

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

According to the RECIST v1.1
3 years follow-up
Rate of patients meeting randomization criteria
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 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.
Tidsramme: 3 year follow-up

As part of a biomarker analysis
3 year follow-up

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Niels Fristrup

Samarbeidspartnere

Aarhus University Hospital

Etterforskere

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

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Generelle publikasjoner

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

6. juli 2020

Primær fullføring (Antatt)

1. desember 2028

Studiet fullført (Antatt)

1. desember 2031

Datoer for studieregistrering

Først innsendt

3. juni 2019

Først innsendt som oppfylte QC-kriteriene

4. juni 2019

Først lagt ut (Faktiske)

6. juni 2019

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

23. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

22. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • NORDIC-SUN

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • CSR

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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