International REgistry of COnservative or Radical Treatment of Localized Kidney Tumors

Kidney Cancer Clinical Trial

— i-RECORd  

Official title:

International REgistry of COnservative or Radical Treatment of Localized Kidney Tumors (i-RECORd)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05363657
• Other study ID #: i-RECORd
• Status: Recruiting
• Start date: January 10, 2022
• Est. completion date: December 31, 2028

Study information

• Verified date: May 2022
• Source: Azienda Ospedaliero-Universitaria Careggi
• Contact: Marco Carini, Prof.
• Phone: 055 794 6351
• Email: carini[@]unifi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Partial nephrectomy (PN) is the standard treatment for localized renal masses and should be preferred in clinical T1 (<7 cm tumor diameter) renal tumors over radical nephrectomy (RN) whenever technically feasible. Nonetheless, indications, approaches, techniques for PN, and correct reporting of outcomes, are still a matter of great debate within the urology community. Concurrently, case-report series suggested that alternative strategies for the treatment of localized renal tumors (ablation techniques (AT), watchful waiting (WW), active surveillance (AS)) could be feasible with acceptable oncologic outcomes in particular settings of patients with localized renal tumors. In this complex clinical scenario, the role surgeon-related and environmental factors (such as surgical experience, hospital resources, countries' social background and performance of health system) are important to address the best personalized approach in patients with renal tumors.

In the light of current evidence, many unsolved questions still remain and many unmet needs must be addressed. In particular, 1) the risk-benefit trade-offs between PN and RN for anatomically complex renal localized tumors; 2) the definition of evidence-based strategies to tailor the management strategy (AT vs WW vs AS vs surgery) in different subset of patients with particular clinical conditions (i.e. old, frail, comorbid patients); and 3) the definition of evidence-based recommendations to adapt surgical approach (open vs laparoscopic vs robotic) and resection techniques to different patient-, tumor-, and surgeon-specific characteristics.

To meet the challenges, to overcome the limitations of current kidney cancer literature (such as the retrospective study design, potential risk of biases, and heterogeneous follow-up of most series), and to provide high-quality evidence for future development of effective clinical practice Guidelines, we designed the international REgistry of COnservative or Radical treatment of localized kiDney tumors (i-RECORD) Project.

The expected impact of the i-RECORD project is to provide robust evidence on the leading clinical and environmental factors driving selection of the management strategy in patients with kidney cancer, and the differential impact of different management strategies (including AS, WW, AT, PN and RN) on functional, perioperative and oncological outcomes, as well as quality of life assessment, at a mid-long term follow-up (5-10 years).

Description:

Study design

The overall objective of the i-RECORD project is to build a multicentre multi-arm multi-stage prospective observational registry collecting data on the management of kidney cancer in consecutive patients treated at 50 tertiary referral Centers worldwide over a 2 years-period and with 5 years of follow-up

. On this registry, six prospective trials with specific objectives have been built.

The i-RECORd project is designed as an observational prospective longitudinal trial involving 50 international, very-high-volume tertiary referral Centers with extensive experience in management of kidney cancer. Centers will be included in the project only if they will be able to certify at least to: 1) perform 150 partial and radical nephrectomy/year, or 2) to perform 80 ATs/year, or 3) to include 50 patients in WW/AS protocols/year.

The enrollment and follow-up periods will be 2 and 5 years, respectively. The estimate of patients' enrollment over the study period is 10'000 inclusions.

The 50 Centers finally enrolled in the i-RECORD project will be given the access to a web-based platform for data collection for 24 months from the starting date of the project.

A web-based e-form platform will be used for data collection.

Data collection

This observational study aims to obtain controlled, qualitative and quantitative, data of the enrolled patients through a web-based e-form platform. For all patients it will be asked to complete a data collection form specifically designed for this study, consisting of some subfolders:

1. Anthropometric, pre-operative and comorbidity data (patient characteristics).

2. Imaging data e and pre-operative tumor features (tumor characteristics).

3. Intra-operative and post-operative data (treatment characteristics).

4. Histopathological analysis (tumor histopathological characteristics).

5. Patients follow-up variables (at 6, 12, 24 and 60 months from the treatment) (follow-up characteristics).

Decision Analysis Modeling

Beyond traditional descriptive and inferential statistical analyses, the i-RECORd project will provide a comprehensive overview of the current selection criteria for each type of management option by applying innovative statistical methods (Decision Analysis Modeling through discrete choice models) to determine the differential impact of all potential relevant variables on the choice of treatment. To do so, we will consider specific clinical scenarios (clinical clusters) made of the integration of patient characteristics (comorbidity score, performance status, age, gender, etc.), patient-reported outcomes measures (PROMs), tumors anatomical features (degree of complexity, clinical diameter, side, location within the kidney, involvement of renal sinus or collecting system, etc.), surgeon-related factors (surgical experience and background), hospital economic availabilities (i.e. open, laparoscopic, robotic surgery) and other country-specific socio-economical features in order to determine the impact of such variables on the final choice of treatment.

By applying the discrete choice model to the analysis of the prospective dataset, the i-RECORd project will overcome the current state of the art in the treatment of localized renal tumors as it will show how the choice of treatment is performed by the decision-maker (at a surgeon- and hospital-level) in each specific clinical cluster of patients, why that choice was performed according to a careful analysis of the personalized patient setting and whether that choice will influence the postoperative outcomes.

Adapted MAMS Registry

The i-RECORD will be designed adapting the innovative concept of multi-arm, multi-stage (MAMS) platform randomized trials (used, for instance, for the design of the Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) Trial) to create a dynamic, observational registry evaluating simultaneously different management options in different patient- and/or tumor-related scenarios.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Radiological diagnosis of renal tumor susceptible to active treatment or AS/WW.

• Age =18 years

• Informed consent signed

Exclusion Criteria:

• Patient refuse to participate in clinical research.

• Urothelial renal carcinoma.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Kidney Cancer
• Kidney Neoplasms

Intervention

Procedure:
• Partial Nephrectomy (PN)
Conservative removal of kidney tumor. The procedure can be performed either with an open or laparoscopic or robotic approach.
• Radical Nephrectomy (RN)
Surgical removal of the affected kidney. Adrenal removal can be performed according to surgeon choice and clinical characteristics of the renal tumor. The procedure can be performed either with an open or laparoscopic or robotic approach.
• Ablation therapy (AT)
The procedure of tumor ablation performed with radiofrequency or cryoablation. The procedure can be performed either with a laparoscopic approach or percutaneous access.

Diagnostic Test:
• Active Surveillance (AS)
Active surveillance is defined as the initial management including the monitoring of renal tumor size by serial imaging with delayed treatment in case of progression.

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Vienna General Hospital	Vienna
Belgium	University of Bruxelles	Bruxelles
Belgium	Onze Lieve Vrouw Hospital	Leuven
Belgium	University Hospitals Leuven	Leuven
Brazil	Santa Casa da Misericórdia de Fortaleza	Fortaleza
Greece	University of Patras	Patras
Italy	Urology, Andrology & Kidney Transplantation Unit, University of Bari	Bari
Italy	Policlinico S. Orsola Malpighi	Bologna
Italy	Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital	Firenze
Italy	Policlinico Riuniti, Università di Foggia.	Foggia
Italy	Division of Urology, University of Genoa,Policlinico San Martino Hospital	Genova
Italy	Azienda Ospedaliera Policlinico "G. Martino", Università di Messina.	Messina
Italy	Policlinico Istituto Europeo di Oncologia (IEO)	Milano
Italy	San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital	Milano
Italy	Istituto Nazionale dei Tumori Fondazione Senatore "G. Pascale"	Napoli
Italy	Institute Oncology Veneto (IOV)	Padova
Italy	Humanitas Hospital	Rozzano
Italy	Università degli studi di Torino, Ospedale Molinette	Torino
Italy	Università degli Studi di Torino, Ospedale S. Luigi Gonzaga.	Torino
Italy	AOUI Verona	Verona
Japan	Jikei University School of Medicine	Tokyo
Netherlands	Amsterdam University Medical Centers	Amsterdam
Poland	European Health Center	Otwock
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie	Warsaw
Russian Federation	N.N. Blokhin National Medical Research Center of Oncology	Moscow
Singapore	NG Teng Fong General Hospital	Singapore
Spain	Fundaciò Puigvert	Barcelona
Spain	Hospital Universitario Ramón y Cajal, University of Alcalá	Madrid
United Kingdom	Bristol Urological Institute	Bristol
United Kingdom	Guy's Hospital	London
United States	Loyola University Medical Center, Edward Hines VA Hospital	Chicago	Illinois
United States	Institute of Urology, University of Southern California.	Los Angeles	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	VCU Health System	Richmond	Virginia
United States	University of California San Diego, Moores Cancer Center	San Diego	California
United States	Swedish Hospital	Seattle	Washington
United States	Stanford University	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Careggi	Italian Group for Advanced Laparo-Endoscopic and Robotic Urologic Surgery (AGILE), Società Italiana di Urologia (SIU)

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Greece,  Italy,  Japan,  Netherlands,  Poland,  Russian Federation,  Singapore,  Spain,  United Kingdom, 

References & Publications (15)

Campbell S, Uzzo RG, Allaf ME, Bass EB, Cadeddu JA, Chang A, Clark PE, Davis BJ, Derweesh IH, Giambarresi L, Gervais DA, Hu SL, Lane BR, Leibovich BC, Pierorazio PM. Renal Mass and Localized Renal Cancer: AUA Guideline. J Urol. 2017 Sep;198(3):520-529. do — View Citation

Finelli A, Ismaila N, Bro B, Durack J, Eggener S, Evans A, Gill I, Graham D, Huang W, Jewett MA, Latcha S, Lowrance W, Rosner M, Shayegan B, Thompson RH, Uzzo R, Russo P. Management of Small Renal Masses: American Society of Clinical Oncology Clinical Pra — View Citation

Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, Barber RM, Barregard L, Bhutta ZA, Brenner H, Dicker DJ, Chimed-Orchir O, Dandona R, Dandona L, Fleming T, Forouzanfar MH, Hancock J, Hay RJ, Hunter-Merrill R, Huynh C, Hosgood HD, Joh — View Citation

Kim SP, Campbell SC, Gill I, Lane BR, Van Poppel H, Smaldone MC, Volpe A, Kutikov A. Collaborative Review of Risk Benefit Trade-offs Between Partial and Radical Nephrectomy in the Management of Anatomically Complex Renal Masses. Eur Urol. 2017 Jul;72(1):6 — View Citation

Larcher A, Fossati N, Tian Z, Boehm K, Meskawi M, Valdivieso R, Trudeau V, Dell'Oglio P, Buffi N, Montorsi F, Guazzoni G, Sun M, Karakiewicz PI. Prediction of Complications Following Partial Nephrectomy: Implications for Ablative Techniques Candidates. Eu — View Citation

Larcher A, Sun M, Dell'Oglio P, Trudeau V, Boehm K, Schiffmann J, Tian Z, Fossati N, Capitanio U, Briganti A, Montorsi F, Karakiewicz P. Mortality, morbidity and healthcare expenditures after local tumour ablation or partial nephrectomy for T1A kidney can — View Citation

Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, Mulders P, Powles T, Staehler M, Volpe A, Bex A. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015 May;67(5):913-24. doi: 1 — View Citation

Mari A, Campi R, Schiavina R, Amparore D, Antonelli A, Artibani W, Barale M, Bertini R, Borghesi M, Bove P, Brunocilla E, Capitanio U, Da Pozzo L, Daja J, Gontero P, Larcher A, Li Marzi V, Longo N, Mirone V, Montanari E, Pisano F, Porpiglia F, Simeone C, — View Citation

Motzer RJ, Jonasch E, Agarwal N, Bhayani S, Bro WP, Chang SS, Choueiri TK, Costello BA, Derweesh IH, Fishman M, Gallagher TH, Gore JL, Hancock SL, Harrison MR, Kim W, Kyriakopoulos C, LaGrange C, Lam ET, Lau C, Michaelson MD, Olencki T, Pierorazio PM, Pli — View Citation

Patel HD, Pierorazio PM, Johnson MH, Sharma R, Iyoha E, Allaf ME, Bass EB, Sozio SM. Renal Functional Outcomes after Surgery, Ablation, and Active Surveillance of Localized Renal Tumors: A Systematic Review and Meta-Analysis. Clin J Am Soc Nephrol. 2017 J — View Citation

Psutka SP, Leibovich BC. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma. Ther Adv Urol. 2015 Aug;7(4):216-29. doi: 10.1177/1756287215576443. Review. — View Citation

Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 30;173(5):489-95. — View Citation

Stewart SB, Thompson RH, Psutka SP, Cheville JC, Lohse CM, Boorjian SA, Leibovich BC. Evaluation of the National Comprehensive Cancer Network and American Urological Association renal cell carcinoma surveillance guidelines. J Clin Oncol. 2014 Dec 20;32(36 — View Citation

Sydes MR, Parmar MK, Mason MD, Clarke NW, Amos C, Anderson J, de Bono J, Dearnaley DP, Dwyer J, Green C, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann G, James ND. Flexible trial design in practice - stopping arms for lack-of-benefit and adding res — View Citation

Volpe A, Blute ML, Ficarra V, Gill IS, Kutikov A, Porpiglia F, Rogers C, Touijer KA, Van Poppel H, Thompson RH. Renal Ischemia and Function After Partial Nephrectomy: A Collaborative Review of the Literature. Eur Urol. 2015 Jul;68(1):61-74. doi: 10.1016/j — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To test the effectiveness of partial nephrectomy for the treatment of localized renal tumors (T1-T2N0M0) with regards to recurrence-free survival and cardiovascular accidents and mortality in comparison to radical nephrectomy?	The preoperative characteristics of the patients will be specifically evaluated to calculate any heterogeneity between the two groups. In detail, anthropometric and comorbidity features, previous abdominal surgery, blood chemistry values, blood pressure, smoking habit, preoperative life expectancy, and frailty grade will be assessed. Imaging features of the tumor will be considered, including the characteristics necessary for the calculation of the PADUA, R.E.N.A.L., and Contact-Surface-Area scores. Patients with a node-positive or metastatic disease diagnosed with conventional imaging (CT scan/MRI) will be excluded. Intra-operative and post-operative outcomes will be evaluated. Histopathological features of the tumor will be assessed.; Patients will be followed up with conventional imaging according to the International guidelines (ultrasound, CT, MRI). Serum creatinine, platelets and estimated glomerular function (eGFR), the onset of cardiovascular adverse events will be registered.	Assesments of the outcome at 60 months from the surgical intervention. Time frame : 5 years
Primary	To test the effectiveness of robotic approach in partial nephrectomy to increase the "Trifecta" rate after nephron-sparing surgery in patients with T1-T2N0M0 renal tumors.	"Trifecta" rate is defined as 1) Absence of intraoperative and postoperative surgical complications; 2) absence of positive surgical margins or recurrences on tumor resection site during a 5-year follow-up; 3) Absence of clinically significant renal function loss at one year after surgery. Renal function will be evaluated using the estimated glomerular filtration rate (eGFR) in ml/min/1.73 m^2 using the CKD-EPI Creatinine Equation (2021). A clinically significant loss will be considered if >25% from eGFR at baseline.; The "Trifecta" outcome will be evaluated one year from surgery.	Assesment of the "Trifecta" outcome will be performed at 12 months from the surgical intervention. Time frame: 1 year.
Secondary	To evaluate the differential impact of patients' comorbidities, tumors' complexity, surgeons' experience, country-related socio-cultural factors and hospital financial resources on the selection of the type of clinical management.	The following variables will be evaluated: Anthropometric, pre-operative and comorbidity data (patient characteristics).; Imaging data and pre-operative tumor features (tumor characteristics).; Centre facilities (laparoscopic/robot assisted, interventional radiology) , volume centre (PN/RN ratio, availability of Multidisciplinary Tumor Board); Intra-operative and post-operative data (treatment characteristics).; Histopathological analysis (tumor histopathological characteristics). The outcome will be considered as the type of clinical management selected: active surveillance (AS) vs ablative treatment (AT) vs partial nephrectomy (PN) vs radical nephrectomy (RN).	Assesment will be done at the time of registering the type of surgery/clinical managing adopted. Time frame: <1 week from patients accrual..
Secondary	To evaluate the impact of the antiaggregant and/or antiplatelet treatment at baseline and during partial nephrectomy on hemorrhagic complications.	The eventual anticoagulant therapy (heparin, warfarin, enoxaparin, fondaparinux) and/or antiplatelet therapy (clopidogrel, ticagrelor, prasugrel, dipyridamole, dipyridamole/aspirin, ticlopidine, eptifibatide) use in patients at baseline and at time of surgery will be assessed.; Hemorrhagic complications (graded according to the "Clavien-Dindo classification") will be evaluated during surgery (intraoperative) and within 90 days (postoperative) with particular attention to the management of hemorrhage (patient monitoring, transfusion, selective embolization, re-intervention with/without kidney removal).	Outcome assesment will be done at 90 days from surgery. Time frame: 3 months
Secondary	To assess in patients with antiaggregant and/or antiplatelet treatment at baseline any potential change of this therapy at the time of treatment associated with the absence of hemorrhagic complications.	The eventual anticoagulant therapy (heparin, warfarin, NAO, enoxaparin, fondaparinux) and/or antiplatelet therapy (clopidogrel, ticagrelor, prasugrel, dipyridamole, dipyridamole/aspirin, ticlopidine, eptifibatide) use in patients at baseline and at time of surgery will be assessed.; Change of treatment from baseline to time of surgery will be considered and specifically evaluated according to the underlying cardio- and/or peripheral- and/or cerebro-vascular diseases.	Outcome assesment will be done at 90 days from surgery. Time frame: 3 months