Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Multiple Primary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

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

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

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

Cytoreductive nephrectomy

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

Tissue sampling

Niels Fristrup, MD PhD

Anne Kirstine Moeller, MD, PhD

Niels Viggo Jensen, MD

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.

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.

Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial

Multicenter Randomized Trial of Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma Receiving Checkpoint Inhibitors: a DaRenCa and NoRenCa Trial Evaluating the Impact of Surgery or No Surgery. The NORDIC-SUN-Trial

Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last 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

Aarhus University Hospital

Niels Fristrup

MD PhD

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Sunitinib 50 mg by mouth daily for 28 consecutive days. Nephrectomy will occur approximately 24 hours after the last dose of sunitinib.

50 mg by mouth daily for 28 consecutive days

Nephrectomy will occur approximately 24 hours after the last dose of sunitinib.

Nephrectomy

Eric Jonasch, MD

The goal of this clinical research study is to learn if Sutent® (sunitinib malate), given before surgery, can help control renal cell carcinoma. The safety of sunitinib malate will also be studied.

The Study Drug:

Sunitinib malate is designed to block pathways that control important events such as the growth of blood vessels that are essential for the growth of cancer.

Study Treatment:

If you are found to be eligible to take part in this study, you will take sunitinib malate once a day (either with or without food) for 4 weeks in a row, followed by 2 weeks of rest with no study drug. These 6 weeks are considered 1 cycle of study treatment.

During Cycle 2, you will have surgery to remove the tumor. You will start taking sunitinib malate again after surgery (at least 14 days after surgery) on the same schedule as before.

Study Visits:

At the beginning of each new cycle (Cycles 1-6), you will have the following tests:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your vital signs, and weight.
* You will have a performance status evaluation.
* You will be asked about any medicines you are currently taking and if you have experienced any side effects since your last visit.
* You will have blood drawn (about 4 teaspoons) for routine testing. This blood will also be tested to check the function of your thyroid gland.
* You will have follow-up scans (the same ones you had during screening to check the disease status) at the beginning of Cycle 2, after you have surgery, and at the beginning of each of the next 4 cycles.
* You will have an ECG to measure the health of your heart.

Every 2 Cycles, you will have a follow-up echocardiogram or MUGA scan to check your heart function, if your doctor feels it is needed.

Beginning in Cycle 7, you will be asked to return to the clinic every other cycle (about every 12 weeks), unless your doctor thinks you should return more often. This means you would return for clinic visits at the start of Cycles 8, 10, 12, and so on, and may be asked to come back at other times.

At each visit, you will have the following tests:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your vital signs and weight.
* You will have a performance status evaluation.
* You will be asked about any medicines you are currently taking and if you have experienced any side effects since your last visit.
* You will have blood drawn (about 4 teaspoons) for routine testing at the beginning of each cycle. If you are scheduled to return to M. D. Anderson every 2 cycles (12 weeks), you may have the blood drawn for routine tests at your local doctor's office during the "non-visit" cycles.
* You will have an ECG to measure the health of your heart.
* You will have an echocardiogram or MUGA scan to check your heart function, if your doctor feels it is needed.
* You will have follow-up scans (the same ones you had during screening to check the disease status).

Length of Study:

You will continue taking sunitinib malate on this study, unless the disease gets worse, you experience intolerable side effects, and/or you need an alternative treatment during the course of the study.

Early Withdrawal:

Early withdrawal is defined as a patient not being able to complete a full cycle of sunitinib malate. If you withdraw early, you will return to clinic for the following tests:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your vital signs, and weight.
* You will have a performance status evaluation.
* You will have blood drawn (about 4 teaspoons) and urine collected for routine testing. This blood will also be tested to check the function of your thyroid gland.
* You will have an ECG to measure the health of your heart.
* You will be asked about any medicines you are currently taking and if you have experienced any side effects since your last visit.
* You will have follow-up scans (the same ones you had during screening to check the disease status).

Post Treatment Evaluation (within 1 month of the last dose):

About 30 days after your last dose of sunitinib malate, you will return to the clinic for a follow-up visit. You will have the following tests:

* Your complete medical history will be recorded.
* You will have a physical exam, including measurement of your vital signs, and weight.
* You will have a performance status evaluation.
* You will have blood drawn (about 4 teaspoons) and urine collected for routine testing. This blood will also be tested to check the function of your thyroid gland.
* You will be asked about any medicines you are currently taking and if you have experienced any side effects since your last visit.
* You will have follow-up scans (the same as at screening) to check the status of the disease.
* You will have an ECG to measure the health of your heart.

Long-Term Follow-Up:

Following the post-treatment visit, you will be contacted regularly to check the status of the disease. You will be contacted (by telephone or routine clinic visit) every 6-12 weeks for the first 2 years, and every 6 months after that for up to 5 years.

This is an investigational study. Sunitinib malate is commercially available and FDA approved for treatment of clear-cell renal cell carcinoma. At this time, its use in combination with surgery is for research only. Up to 50 patients will take part in this study. All will be enrolled at MD Anderson.

Pre-Surgical Sutent in Renal Cell Carcinoma (RCC)

Phase II Non-Randomized Pre-Surgical Study Evaluating Sunitinib in Patients With Metastatic Renal Cell Carcinoma (RCC) Who Are Eligible for Cytoreductive Nephrectomy

TTP is defined as the time interval between treatment starts and disease progression or death, whichever occurred first, assessed each cycle (42 days).

Toxicity defined as any Grade 3 or greater perioperative complications attributable to sunitinib.

Pfizer

M.D. Anderson Cancer Center

Immune Checkpoint Inhibitors

Axitinib

Preoperative Treatment with Toripalimab: Administer 240mg of Toripalimab via intravenous infusion every 3 weeks for a total of 4 cycles.

Toripalimab

Radical Nephrectomy: Complete resection of the tumor and affected kidney within the renal fascia.

Partial Nephrectomy: Complete resection of the tumor while preserving maximal kidney function.

Lymph Node Dissection: For patients with evident enlargement of retroperitoneal lymph nodes preoperatively, perform lymph node dissection at the renal hilum, along the ipsilateral major vessels, and anterior to the ipsilateral major vessels. Lymph node dissection is not required for patients without evident enlargement of retroperitoneal lymph nodes preoperatively.

Cytoreductive Nephrectomy

Preoperative Treatment with Axitinib: Administer 5mg of axitinib orally twice daily for a duration of 3 months.

Study Objective: To determine the efficacy of upfront immune checkpoint inhibitors combined with deferred cytoreductive nephrectomy in treating metastatic renal cell carcinoma.

Primary Endpoint: Pathological Major Response (MPR), defined as the percentage of residual tumor cells \<10% in the primary tumor after nephrectomy.

Study Design:

Population: Participants meeting the diagnostic criteria with biopsy-proven clear cell renal cell carcinoma, IMDC score ≤3, or ≤5 metastatic lesions involving ≤3 organs.

Sample Size: 20 participants.

Patient Grouping: Non-randomized.

Interventions: Eligible participants will receive upfront treatment with a combination of Axitinib and Toripalimab for 4 cycles. After 2 cycles of treatment, radiological assessment will be conducted using RECIST 1.1 criteria. If disease progression is observed, the clinical trial will be terminated, and second-line treatment will be initiated according to guidelines. If disease progression is not observed, treatment will continue for 2 additional cycles followed by repeat radiological assessment before undergoing surgery.

Upfront Immune Checkpoint Inhibitors With Deferred Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma

Upfront Toripalimab Plus Axitinib Combined With Deferred Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma

The percentage of residual tumor cells in the primary tumor after surgery, with MPR defined as less than 10% of residual tumor cells in the pathology report.

RenJi Hospital

sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously

Cytoreductive nephrectomy + sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously

sunitinib or pazopanib

Cytoreductive nephrectomy and first-line treatment

Giuseppe Procopio, MD

Two randomized trials in the cytokine era clearly showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC) increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs) including first-line sunitinib and pazopanib in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy.

Therefore it is unknown if similar survival benefit could be achieved without CN with these new targeted agents.

At the same time there is a need to better understand mechanisms of primary and secondary resistance to TKIs in mRCC patients and to identify eighter prognostic and predictive biomarkers to better define risk factors and potentially druggable targets.

Two randomized trials in the cytokine era clearly showed that CN had a role in mRCC increasing life expectancy. The survival benefit of TKIs including first-line sunitinib and pazopanib in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy.Therefore it is unknown if similar survival benefit could be achieved without CN with these new targeted agents.

At the same time there is a need to better understand mechanisms of primary and secondary resistance to TKIs in mRCC patients and to identify eighter prognostic and predictive biomarkers to better define risk factors and potentially druggable targets.

The hypothesis of this study is that CN followed by TKIs will improve overall survival (OS) when compared to TKIs alone in subjects with mRCC. Circulating blood biomarkers (CBBs) promise to become non-invasive real-time surrogates for tissue-based biomarkers. Circulating tumor cells (CTCs) shed from both primary tumors and metastases, and circulating tumor DNA (ctDNA) released into the bloodstream from dying tumor cells, are likely to capture the entire tumor heterogeneity providing a clear picture of the tumor genetic landscape. Moreover, CTCs fluctuations reflect and possibly anticipate treatment outcome. Through comparison of CBBs before and after disease becomes refractory to therapy, the investigators would be able to address challenging research questions regarding TKIs resistance mechanisms.

This study was designed to compare clinical benefit as measured by Overall Survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety provided by CN followed by TKIs vs upfront TKIs in mRCC subjects.To prospectively collect blood samples from patients at commencement of TKIs therapy and on development of resistance, with the purpose of analyzing CTCs and ctDNA mutational profile to highlight mechanisms underlying TKIs resistance. The investigators additionally aim to assess the role of CTCs as prognostic and pharmacodynamic biomarkers and prospectively collect demographic and clinical outcome data so that molecular and pathological analyses can be measured against clinical endpoints.

Rationale for TKIs treatment choice:

Pazopanib and sunitinib were compared to each other as a therapy for previously untreated patients with mRCC within the phase 3 non inferiority COMPARZ trial which represented the first-ever head-to-head comparison of first-line treatments for mRCC. Overall, the median PFS and OS with pazopanib compared to sunitinib were statistically non-inferior, showing that both agents are active and provide similar high quality care. For this reason the TKI will be assigned based on patients characteristics according to the guidelines of every single institution involved in the study.

Statistical plan:

The sample size was calculated in order to compare 5-year OS between subjects randomized to receive CN followed by TKIs and subjects randomized to receive TKIs (main study endpoint). A total of 191 deaths will yield 80% power to detect a hazard ratio of 1.5 of TKIs vs. CN followed by TKIs with an overall type 1 error of 0.05 (two-sided log-rank test). Such a hazard ratio (HR) corresponds to an increase in the 5-year OS, from an anticipated value 10% for TKIs to 21.5% for CN followed by TKIs. The investigators estimate that approximately 270 patients (135 in each arm), recruited over 3 years and with a minimum follow up of 2 years, will be necessary to see the necessary number of deaths.

An interim analysis of OS based on O'Brien-Fleming stopping rules is planned at 96 deaths at approximately 34 months after randomisation.

Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery

To explore the association between baseline CTCs count and OS or PFS

To compare baseline CTCs count and CTCs at the time of RECIST 1.1 PD on TKIs therapy, with the aim of better understand progressive changes in the tumor as resistance develops

To compare clinical benefit, as measured by Overall Survival (OS), provided by CN followed by TKIs vs upfront TKIs in subjects with mRCC

To compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs

Safety profile of cytoreductive nephrectomy with TKIs vs upfront TKIs. (according to Common Terminology Criteria for Adverse Events -CTCAE- v 4.03). All Adverse events will be reported according to National Cancer Institute Criteria. The incidence of adverse events will be summarized according to the primary system-organ class (SOC) and within the category defined in the CTCAE v4.03. The summaries will be overall (severity grades 1-4) and for grade ≥3 events and will also report the actions taken in terms of treatment discontinuation. Similar summaries will be made for serious adverse events. The safety set will be considered.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Pembrolizumab

Avelumab

Immunomodulating Agents

Nivolumab 240 mg IV 1 q 2 weeks

OR

Nivolumab 480 mg IV 1 q 4 weeks

OR

Pembrolizumab 200 mg IV 1 q 3 weeks Axitinib 5 mg oral Daily BID

OR

Avelumab 10 mg/kg IV 1 q 2 weeks Axitinib 5 mg oral Daily BID

Continued systemic therapy as above, plus:

Radical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization.

Radical or partial nephrectomy may be performed using laparoscopic, open, or robotic approaches. Surgery should be performed within 8 weeks of randomization

Active Comparator

Megan Keim, MS

Dana Sparks, MAT

Site Public Contact

Arnab Basu

Chinedu Mmeje

John A. Ellerton

Benjamin R. Lee

Jay W. Carlson

Ari D. Baron

Varsha Tulpule

Abhishek Tripathi

Hyung L. Kim

Brian Shuch

Shuchi Gulati

Suthee Rapisuwon

Carlos A. Alemany

Daniel Landau

Priyank P. Patel

Adam P. Siegel

Bryan A. Faller

Joseph I. Clark

Jeffrey A. Sosman

Alan Tan

Daniel Moreira

Brian C. Myre

This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.

PRIMARY OBJECTIVE:

I. To compare overall survival in participants with newly diagnosed metastatic renal cell carcinoma who are randomized to receive immune checkpoint inhibitor-based combination treatment plus cytoreductive nephrectomy versus immune checkpoint inhibitor-based combination treatment alone.

SECONDARY OBJECTIVES:

I. To compare overall survival between arms in the subset who received their assigned protocol treatment.

II. To assess complications of nephrectomy and post-randomization drug toxicities.

III. To compare objective response rate in metastatic sites between the arms in participants with measurable metastatic disease.

IV. To assess change in diameter of primary tumor at week 12 disease assessment in participants who have received pre-randomization treatment.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE:

PRE-RANDOMIZATION TREATMENT: Treatment naive patients are assigned to 1 of 3 treatment regimens per standard of care.

REGIMEN I: Patients receive nivolumab intravenously (IV) and ipilimumab IV. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV on day 1. Cycles repeat every 2-4 weeks in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive pembrolizumab IV on day 1 and axitinib orally (PO) twice daily (BID) on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

REGIMEN III: Patients receive avelumab IV on day 1 and axitinib PO BID on days 1-14. Cycles repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: Some patients may have already completed the standard of care pre-randomization treatment specified above off-trial.

RANDOMIZATION TREATMENT: Between 10-14 weeks from the start of on-trial or off-trial pre-randomization treatment, patients are randomized to 1 of 2 arms.

ARM I: Patients receive nivolumab IV, pembrolizumab IV, or avelumab IV on day 1. Patients also receive axitinib PO BID. Cycles with nivolumab repeat every 2 or 4 weeks, cycles with pembrolizumab repeat every 3 weeks, and cycles with avelumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Within 42 days following randomization, patients undergo radical or partial nephrectomy in addition to nivolumab, pembrolizumab, avelumab, and axitinib as in Arm I in the absence of disease progression or unacceptable toxicity. Axitinib should be stopped at least 24 hours prior to surgery.

After completion of trial treatment, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, and then annually for up to 7 years from randomization.

Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial

Phase III Trial of Immunotherapy-Based Combination Therapy With or Without Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma (PROBE Trial)

Analysis will be intent-to-treat. Evidence suggesting early termination of the trial and a conclusion that the cytoreductive nephrectomy (CN) approach is superior to treatment alone would be if the null hypothesis is rejected at the one-sided 0.005 level. For the second and third interim analyses, the null and alternative hypotheses with respect to survival will be tested, with superiority tested at the one-sided 0.005 level, and futility determined to be met if the (CN versus no CN) hazard ratio is greater than or equal to 1. A proportional hazards model will be fit to estimate the hazard ratio adjusting for the stratification factors as covariates in the model. Will evaluate whether each of the stratification factors are predictive factors of cytoreductive nephrectomy by placing an interaction term corresponding to each stratification factor and treatment arm in the proportional hazards survival model.

Will be included in the proportional hazards regression model adjusting for stratification factors as covariates.

A proportional hazards model will be used to compare progression-free survival between arms, adjusting for the stratification factors as covariates.

Objective response includes all confirmed and unconfirmed partial and complete responses. Baseline will be disease assessment at randomization. Response Evaluation Criteria in Solid Tumors response rates will be evaluated, excluding the primary tumor in the kidney because that disease will be removed in half the participant's post-randomization. Comparison of response rates will be performed using logistic regression with stratification factors as covariates and an indicator for treatment arm.

Descriptive statistics will be provided including stratified results by treatment regimen received. Potential additional analyses may include assessment of the interaction between change in primary tumor and randomized treatment arm. This will be modeled as an interaction term in the proportional hazards survival model.

National Cancer Institute (NCI)

SWOG Cancer Research Network

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Cytoreductive Nephrectomy within 6 months to 1 year after start systemic therapy for metastatic Renal Cell Carcinoma

Standard of Care for metastatic Renal Cell Carcinoma

The experimental intervention consists of cytoreductive nephrectomy (CN) or any ablative local therapy within 6 months and 1 year after start of systemic treatment. All types of ablative local therapy are allowed as a substitute for CN

Adriaan Bins, MD PhD

Axel Bex, MD PhD

The benefit of deferred Cytoreductive Nephrectomy (CN) has to be re-assessed in the context of IO +IO and IO + TKI systemic treatment. Given the benefit of CN in the setting of first generation immunotherapy, it is conceivable that both trials underestimated the benefit of CN, in absence of immunotherapy.

In past years, much research has been done into the beneficial effects of cytoreductive nephrectomy in patients with metastatic renal cancer receiving systemic therapy with positive results. In the meantime systhemic therapy, and in particular immunotherapy, have changed. Patients with metastatic renal cancer are increasingly treated with immunocheckpoint inhibitors, but the effect of adding cytoreductive nephrectomy in this group of patients has not yet been investigated. The aim of this study is to investigate whether performing a cytoreductive nephrectomy has a beneficial effect on overall survival in patients with metastatic renal cancer receiving systemic therapy using immunocheckpoint inhibitors.

A randomized controlled trial. All eligible patients have already been enrolled in the PRO-RCC registry, a registry that collects prospective observational data, and have also given consent to be included in other studies as a control cohort. This design is called a TWiC (trial within cohort). After randomization, patients who are randomized into the therapy arm will receive a patient information via their treating physician. Upon participation, an informed consent will be signed and the patient will be scheduled for surgery.

Primary Metastatic Renal Cell Carcinoma Treated With Immunecheckpoint Inhibitors and Cytoreductive Nephrectomy

A Prospective Study of Primary Metastatic Renal Cell Carcinoma Treated With Immunecheckpoint Inhibitors and Cytoreductive Nephrectomy vs Primary Tumour in Place

In detail, we will examine the intratumor alteration of tumor infiltrating CD8, CD4, NK(T) cells (CD56+,CD3+-), and the distribution of these NK cells in the tumor, as these cells have been shown to be involved in anti-tumor responses in RCC.

Overall Survival Using Kaplan Meier Survival analysis

using the Dutch validated EORTC Quality of Life Questionnaire (QLQ-C30)

Clavien Dindo classification of surgical morbidity is used to classify morbidity outcomes

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial	NCT03977571	Kidney Cancer Renal Cell Carc... Synchronous Neo...	Cytoreductive n... Tissue sampling	18 Years -	University of Aarhus
Pre-Surgical Sutent in Renal Cell Carcinoma (RCC)	NCT00715442	Renal Cell Carc...	Sunitinib Nephrectomy	-	M.D. Anderson Cancer Center
Upfront Immune Checkpoint Inhibitors With Deferred Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma	NCT06279403	Clear-cell Meta... Immune Checkpoi... Cytoreductive N...	Toripalimab Cytoreductive N... Axitinib	18 Years - 80 Years	RenJi Hospital
Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery	NCT02535351	Clear-cell Meta...	sunitinib or pa... Cytoreductive n...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Upfront Immune Checkpoint Inhibitors With Deferred Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma	NCT06279403	Clear-cell Meta... Immune Checkpoi... Cytoreductive N...	Toripalimab Cytoreductive N... Axitinib	18 Years - 80 Years	RenJi Hospital
Pre-Surgical Sutent in Renal Cell Carcinoma (RCC)	NCT00715442	Renal Cell Carc...	Sunitinib Nephrectomy	-	M.D. Anderson Cancer Center
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial	NCT04510597	Metastatic Clea... Metastatic Rena... Stage IV Renal ...	Cytoreductive N... Active Comparat...	18 Years -	SWOG Cancer Research Network
Primary Metastatic Renal Cell Carcinoma Treated With Immunecheckpoint Inhibitors and Cytoreductive Nephrectomy	NCT05941169	Renal Cell Carc...	Cytoreductive N...	18 Years -	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Spots Global Cancer Trial Database for cytoreductive nephrectomy