NCT03977571

Brief Summary

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.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
400

participants targeted

Target at P75+ for not_applicable

Timeline
68mo left

Started Jul 2020

Longer than P75 for not_applicable

Geographic Reach
2 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress51%
Jul 2020Dec 2031

First Submitted

Initial submission to the registry

June 3, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 6, 2019

Completed
1.1 years until next milestone

Study Start

First participant enrolled

July 6, 2020

Completed
8.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2028

Expected
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2031

Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

8.4 years

First QC Date

June 3, 2019

Last Update Submit

April 28, 2026

Conditions

Kidney CancerSynchronous NeoplasmRenal Cell Carcinoma Metastatic

Keywords

Cytoreduction Surgical ProceduresNephrectomyIpilimumabNivolumabLaboratory biomarker analysisGene ExpressionLiquid Biopsy

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    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

Secondary Outcomes (12)

  • Progression free survival

    3 years follow-up

  • Time to subsequent systemic therapy

    3 years follow-up

  • Objective response rate

    3 years follow-up

  • Rate of patients meeting randomization criteria

    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

    3 years follow-up

  • +7 more secondary outcomes

Study Arms (2)

Deferred nephrectomy

EXPERIMENTAL

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

Procedure: Cytoreductive nephrectomyOther: Tissue sampling

No surgery

ACTIVE COMPARATOR

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

Other: Tissue sampling

Interventions

Cytoreductive nephrectomyPROCEDURE

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

Deferred nephrectomy
Tissue samplingOTHER

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

Deferred nephrectomyNo surgery

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)
  • +1 more criteria

You may not qualify if:

  • Prior systemic treatment for mRCC
  • Other cancer within 3 years (except in situ basal cell carcinoma and localised prostate cancer with undetectable PSA).
  • Major surgical procedure, open surgical biopsy, or significant traumatic injury within 28 days prior to enrollment
  • No symptomatic brain metastasis requiring systemic corticosteroids (\> 10 mg daily prednisone equivalent)
  • 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.
  • Oral or i.v. antibiotics administered 14 days prior to initiation of systemic therapy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Department of Oncology, Aarhus University Hospital

Aarhus, Central Region of Denmark, 8200, Denmark

RECRUITING

Department of Oncology, Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

Department of Oncology, Odense University Hospital

Odense, 5000, Denmark

RECRUITING

Department of Oncology, Ålesund Universitetsykehus

Ålesund, Norway

RECRUITING

Department of Urology, Haukeland University Hospital

Bergen, Norway

RECRUITING

Department of Oncology, Stavanger Universitetssykehus

Stavanger, Norway

RECRUITING

Related Publications (3)

  • Flammia RS, Campi R, Bologna E, Bertolo R, Leonardo C, Calabro F, Amparore D, Simone G; Young Academic Urologists (YAU) Renal Cancer Working Group. Cytoreductive nephrectomy in the era of immune-checkpoint inhibitors: back to the future? BJU Int. 2026 Feb 11. doi: 10.1111/bju.70168. Online ahead of print.

    PMID: 41673778DERIVED

  • Iisager L, Ahrenfeldt J, Donskov F, Ljungberg B, Bex A, Lund L, Lyskjaer I, Fristrup N. Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial. BMC Cancer. 2024 Feb 24;24(1):260. doi: 10.1186/s12885-024-11987-3.

    PMID: 38402173DERIVED

  • Kuusk T, Abu-Ghanem Y, Mumtaz F, Powles T, Bex A. Perioperative therapy in renal cancer in the era of immune checkpoint inhibitor therapy. Curr Opin Urol. 2021 May 1;31(3):262-269. doi: 10.1097/MOU.0000000000000868.

    PMID: 33742979DERIVED

MeSH Terms

Conditions

Kidney NeoplasmsNeoplasms, Multiple Primary

Condition Hierarchy (Ancestors)

Urologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteNeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Study Officials

  • Niels Fristrup, MD PhD

    Department of Oncology, Aarhus University Hospital.

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Niels Fristrup, MD PhD

CONTACT

004520914161niels.fristrup@rm.dk

Ane Iversen, MD PhD

CONTACT

ANEIVE@rm.dk

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD PhD

Study Record Dates

First Submitted

June 3, 2019

First Posted

June 6, 2019

Study Start

July 6, 2020

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2031

Last Updated

May 4, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share
Shared Documents
STUDY PROTOCOL, CSR

Locations

NO(3)DK(3)