Clear-cell Metastatic Renal Cell CarcinomaPhase 3TARIBONCT02535351
Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery
A Phase 3 study testing sunitinib or pazopanib and Cytoreductive nephrectomy in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Clear-cell Metastatic Renal Cell Carcinoma
- What is being tested?
- sunitinib or pazopanib and Cytoreductive nephrectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2015to 28 Sep 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent
- ECOG Performance Status 0-1
- Favorable or intermediate MSKCC or Heng risk score
- Biopsy (primary tumour or metastases) confirming the diagnosis of predominantly clear cell RCC
- Resectable asymptomatic in situ primary (asymptomatic primary is defined as the absence of symptoms which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion.)
- Tumour suitable to nephrectomy in the opinion of the urologist. Patients with Inferior vena cava thrombosis can be included
Show all 17Show fewer
- Documented metastatic disease (CT scan or MRI)
- Life expectancy > or = 24 weeks
- Up to three different metastatic sites
- ≥ 3 metastatic lesions
- Platelets > 100,000/ml
- Haemoglobin > 9.0 g/dl
- neutrophils >1,500/mm3
- Bilirubin < or = 2 mg/dl, except for patients affected by Gilbert's syndrome
- AST and ALT < or = 2.5 times the UNL
- Serum albumin > the LNL
- Patients of childbearing age should use contraceptive methods during the study
Who cannot join
- Prior surgery or systemic treatment for mRCC
- Bilateral RCC
- Brain and liver metastases
- Non-clear-cell histology
- Poor prognosis as defined by MSKCC or Heng criteria
- Documented widespread disease (> or =4 metastatic organ sites)
Show all 22Show fewer
- Oligometastatic disease suitable of metastasectomy (<3 lesions confined at one organ site)
- Symptomatic primary tumour at presentation
- High surgical risk in the opinion of the urologist
- Patients with > 3 of the following surgical risk factors are not eligible:
- Serum albumin CTCAE v 4.0 grade 2 or worse
- Serum LDH > 1.5 times upper limit of normal
- Symptoms at presentation due to metastases
- Clinical stage T4 disease
- History of malabsorption syndrome
- Pregnant or breastfeeding women
- Concomitant cardiac disorders: cardiac failure NYHA> 2; Acute coronary syndrome or myocardial infarction or severe or unstable angina within the last 6 months as well as uncontrolled hypertension (sistolic>160, diastolic>90), arrhytmia requiring treatment (except for beta blockers or digossin)
- Uncontrolled diabetes
- Deep phlebitis not treated with LMWH or arterial thrombosis within the last 6 months
- HIV infection
- Active infections (> Grade 2 NCI-CTC v.3.0)
- Other cancer within the previous 5 years (except for in situ skin carcinoma, superficial bladder Ta, Tis, T1 and carcinoma of the cervix or every cancer with curative treatment within 5 years)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
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.
- Being tested
- sunitinib or pazopanib, Cytoreductive nephrectomy
- Keywords
- Clear cell Metastatic renal cell carcinoma, Cytoreductive nephrectomy, First line treatment
- Medical subject headings
- Clear-cell metastatic renal cell carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sunitinib or pazopanibDrug
Also called sutent or votrient
First-line treatment
Cytoreductive nephrectomyProcedure or surgery
Cytoreductive nephrectomy and first-line treatment
| Study group | Role | What they receive |
|---|---|---|
| A: TKIs | Active comparator | sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously Receives: Drug: sunitinib or pazopanib |
| B: TKIs + Cytoreductive Nephrectomy | Experimental | Cytoreductive nephrectomy + sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously Receives: Drug: sunitinib or pazopanib; Procedure: Cytoreductive nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs in subjects with mRCC
To compare clinical benefit, as measured by Overall Survival (OS), provided by CN followed by TKIs vs upfront TKIs in subjects with mRCC
Measured: 5 years
Secondary outcomes (2)
Progression-free survival (PFS) and response rate (RR) benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs
To compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs
Measured: Radiological assessment: every 12 weeks (±1 week) until Progressive disease (up to 12 months) or treatment discontinuation (up to 5 years)
Safety profile (Adverse events)
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.
Measured: day 1, every cycle (6 weeks for patients treated with Sunitinib and 4 weeks for patients treated with Pazopanib) until treatment discontinuation (up to 5 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2015 (estimated)
- Study startNov 2015
- Primary completion28 Sep 2018
- Study completion28 Sep 2018
Why it stopped: low enrolment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Clear-cell Metastatic Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giuseppe Procopio, MD, Principal investigator, Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02535351
- Sponsor's protocol ID
- INT 75/15
- Other IDs
- 2015-002240-14, 2015
- Acronym
- TARIBO
- Status last verified
- Nov 2018
- First submitted
- 4 Aug 2015
- Last updated
- 14 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Flanigan RC, Yonover PM. The role of radical nephrectomy in metastatic renal cell carcinoma. Semin Urol Oncol. 2001 May;19(2):98-102.
PubMed 11354539Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. doi: 10.1056/NEJMoa003013.
PubMed 11759643Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. doi: 10.1016/s0140-6736(01)06103-7.
PubMed 11583750Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004 Mar;171(3):1071-6. doi: 10.1097/01.ju.0000110610.61545.ae.
PubMed 14767273Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989.
PubMed 23964934Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, McDermott DF, Rini BI, Heng DY. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 2011 Jan;185(1):60-6. doi: 10.1016/j.juro.2010.09.012. Epub 2010 Nov 12.
PubMed 21074201Gossage L, Murtaza M, Slatter AF, Lichtenstein CP, Warren A, Haynes B, Marass F, Roberts I, Shanahan SJ, Claas A, Dunham A, May AP, Rosenfeld N, Forshew T, Eisen T. Clinical and pathological impact of VHL, PBRM1, BAP1, SETD2, KDM6A, and JARID1c in clear cell renal cell carcinoma. Genes Chromosomes Cancer. 2014 Jan;53(1):38-51. doi: 10.1002/gcc.22116. Epub 2013 Oct 29.
PubMed 24166983Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, Pal SK, Kollmannsberger CK, Yuasa T, Srinivas S, Donskov F, Bamias A, Wood LA, Ernst DS, Agarwal N, Vaishampayan UN, Rha SY, Kim JJ, Choueiri TK. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014 Oct;66(4):704-10. doi: 10.1016/j.eururo.2014.05.034. Epub 2014 Jun 13.
PubMed 24931622Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
PubMed 32203306
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery
- ClinicalTrials.gov ID
- NCT02535351
- Acronym / sponsor ID
- TARIBO / INT 75/15
- Keywords
- Clear cell Metastatic renal cell carcinoma, Cytoreductive nephrectomy, First line treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low enrolment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, MilanoUniversity, hospital or other
- Study start
- Nov 2015 (actual)
- Primary completion
- 28 Sep 2018 (actual)
- Study completion
- 28 Sep 2018 (actual)
- First posted
- 28 Aug 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: TKIs | Active comparator | Drug: sunitinib or pazopanibsunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously |
| B: TKIs + Cytoreductive Nephrectomy | Experimental | Drug: sunitinib or pazopanib, Procedure: Cytoreductive nephrectomyCytoreductive nephrectomy + sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent
- ECOG Performance Status 0-1
- Favorable or intermediate MSKCC or Heng risk score
- Biopsy (primary tumour or metastases) confirming the diagnosis of predominantly clear cell RCC
- Resectable asymptomatic in situ primary (asymptomatic primary is defined as the absence of symptoms which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion.)
Key exclusion criteria (22 listed)
- Prior surgery or systemic treatment for mRCC
- Bilateral RCC
- Brain and liver metastases
- Non-clear-cell histology
- Poor prognosis as defined by MSKCC or Heng criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sunitinib or pazopanibAlso: sutent or votrientFirst-line treatment | Drug | A: TKIs, B: TKIs + Cytoreductive Nephrectomy |
| Cytoreductive nephrectomyCytoreductive nephrectomy and first-line treatment | Procedure or surgery | B: TKIs + Cytoreductive Nephrectomy |
Primary outcome
Overall Survival benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs in subjects with mRCC
Time frame: 5 years
To compare clinical benefit, as measured by Overall Survival (OS), provided by CN followed by TKIs vs upfront TKIs in subjects with mRCC
2 secondary outcomes
Progression-free survival (PFS) and response rate (RR) benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs
Time frame: Radiological assessment: every 12 weeks (±1 week) until Progressive disease (up to 12 months) or treatment discontinuation (up to 5 years)
Safety profile (Adverse events)
Time frame: day 1, every cycle (6 weeks for patients treated with Sunitinib and 4 weeks for patients treated with Pazopanib) until treatment discontinuation (up to 5 years).
Results and safety
The study was stopped early (reason given: low enrolment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- Background: PubMed 11354539Flanigan RC, Yonover PM. The role of radical nephrectomy in metastatic renal cell carcinoma. Semin Urol Oncol. 2001 May;19(2):98-102.
- Background: PubMed 11759643Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. doi: 10.1056/NEJMoa003013.
- Background: PubMed 11583750Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. doi: 10.1016/s0140-6736(01)06103-7.
- Background: PubMed 14767273Flanigan RC, Mickisch G, Sylvester R, Tangen C, Van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis. J Urol. 2004 Mar;171(3):1071-6. doi: 10.1097/01.ju.0000110610.61545.ae.
- Background: PubMed 23964934Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013 Aug 22;369(8):722-31. doi: 10.1056/NEJMoa1303989.
- Background: PubMed 21074201Choueiri TK, Xie W, Kollmannsberger C, North S, Knox JJ, Lampard JG, McDermott DF, Rini BI, Heng DY. The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 2011 Jan;185(1):60-6. doi: 10.1016/j.juro.2010.09.012. Epub 2010 Nov 12.
- Background: PubMed 24166983Gossage L, Murtaza M, Slatter AF, Lichtenstein CP, Warren A, Haynes B, Marass F, Roberts I, Shanahan SJ, Claas A, Dunham A, May AP, Rosenfeld N, Forshew T, Eisen T. Clinical and pathological impact of VHL, PBRM1, BAP1, SETD2, KDM6A, and JARID1c in clear cell renal cell carcinoma. Genes Chromosomes Cancer. 2014 Jan;53(1):38-51. doi: 10.1002/gcc.22116. Epub 2013 Oct 29.
- Background: PubMed 24931622Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, Pal SK, Kollmannsberger CK, Yuasa T, Srinivas S, Donskov F, Bamias A, Wood LA, Ernst DS, Agarwal N, Vaishampayan UN, Rha SY, Kim JJ, Choueiri TK. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014 Oct;66(4):704-10. doi: 10.1016/j.eururo.2014.05.034. Epub 2014 Jun 13.
- Derived from this study: PubMed 32203306Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Procopio, MD principal investigator
Fondazione IRCCS ISTITUTO NAZIONALE TUMORI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing sunitinib or pazopanib and Cytoreductive nephrectomy in people with Clear-cell Metastatic Renal Cell Carcinoma, run by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: low enrolment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival benefit of cytoreductive nephrectomy with TKIs vs upfront TKIs in subjects with mRCC (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02535351, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2018.