Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma
RECORD-3
An Open-label, Multicenter Phase II Study to Compare the Efficacy and Safety of RAD001 as First-line Followed by Second-line Sunitinib Versus Sunitinib as First-line Followed by Second-line RAD001 in the Treatment of Patients With Metastatic Renal Cell Carcinoma.
2 other identifiers
interventional
471
19 countries
84
Brief Summary
This study assessed the efficacy and safety of first-line RAD001 followed by second-line sunitinib versus the opposite sequence: first-line sunitinib followed by second-line RAD001 for the treatment of patients with MRCC.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2009
Longer than P75 for phase_2
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 24, 2009
CompletedFirst Posted
Study publicly available on registry
May 18, 2009
CompletedStudy Start
First participant enrolled
October 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedResults Posted
Study results publicly available
June 28, 2016
CompletedNovember 8, 2016
October 1, 2016
5.6 years
April 24, 2009
May 20, 2016
October 4, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival First-Line (PFS 1-L)
PFS\_1L based on investigator assessment of radiology data by RECIST 1.0, was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause during or after first-line treatment with everolimus or sunitinib. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Secondary Outcomes (12)
Progression-free Survival Combined (PFS-C)
based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to about 56 months
Overall Survival (OS)
Every 2 months from randomization up to 3 years after last patient randomized
Overall Response Rate (ORR) - First -Line (1-L)
based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Duration of Response (DoR) - First-Line (1-L)
based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months
Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug
<=14 days prior to the first dose of study medication, on day 1, day 28 of every cycle, at the end of treatment visit, at the 28 day FUP visit and monthly thereafter for up to 3 months or until initiation of another anticancer therapy up to 35 months
- +7 more secondary outcomes
Study Arms (2)
everolimus 1L/sunitinib 2L
EXPERIMENTALeverolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
sunitinib 1L/everolimus 2L
ACTIVE COMPARATORsunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Interventions
Everolimus was administered orally at 10 mg/day. Everolimus is formulated as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets.
Sunitinib was administered orally 50 mg daily, on a schedule of 4 weeks on/2 weeks off. Sunitinib was supplied as hard gelatin capsules of 12.5 mg, 25 mg, or 50 mg strength according to local practice.
Eligibility Criteria
You may qualify if:
- Patients with advanced renal cell carcinoma.
- Patients with at least one measurable lesion.
- Patients with a Karnofsky Performance Status ≥70%.
- Adequate bone marrow function.
- Adequate liver function.
- Adequate renal function.
- Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
- Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. Adequate contraception must be used while on study.
You may not qualify if:
- Less than 4 weeks post-major surgery
- Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start).
- Patients in need for major surgical procedure during the course of the study
- Patients with a serious non-healing wound, ulcer, or bone fracture
- Patients with a history of seizure(s) not controlled with standard medical therapy
- Patients who have received prior systemic treatment for their metastatic RCC
- Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy, vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients
- Patients with a known hypersensitivity to sunitinib or its excipients
- History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:
- Are asymptomatic and,
- have had no evidence of active CNS metastases for ≥ 6 months prior to enrollment and,
- have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)
- Clinically significant gastrointestinal abnormalities including, but not limited to:
- Malabsorption syndrome
- +22 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (84)
University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)
Birmingham, Alabama, 35294-0006, United States
University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
Mobile, Alabama, 36688, United States
Highlands Oncology Group HighlandsOncGrp-Bentonville(2)
Fayetteville, Arkansas, 72703, United States
University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
La Jolla, California, 92093-0658, United States
University of California at Los Angeles Dept. of UCLA (3)
Los Angeles, California, 90095, United States
University of Colorado Dept. of Anschutz Cancer (2)
Aurora, Colorado, 80045, United States
Norwalk Hospital Norwlak SC
Norwalk, Connecticut, 06856, United States
Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2
Washington D.C., District of Columbia, 20007-2197, United States
Lynn Cancer Institute
Boca Raton, Florida, 33486, United States
University of Miami SC
Miami, Florida, 33136, United States
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando
Orlando, Florida, 32806, United States
University Cancer & Blood Center, LLC Dept of NE GCC (2)
Athens, Georgia, 30607, United States
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, 30912, United States
Summit Cancer Care
Savannah, Georgia, 31405, United States
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital
Chicago, Illinois, 60611, United States
Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)
Maywood, Illinois, 60153, United States
Crescent City Research Consortium, LLC SC
Metairie, Louisiana, 70006, United States
VA Maryland Health Care Dept.of GreenbaumCancerCent(7)
Baltimore, Maryland, 21201, United States
Weinberg Cancer Institute at Franklin Square Hospital
Baltimore, Maryland, 21237-3998, United States
Billings Clinic Dept of Billings Clinic(2)
Billings, Montana, 59107, United States
Hackensack University Medical Center DeptofHackensackUniv.MedCtr.
Hackensack, New Jersey, 07601, United States
Cooper Cancer Center
Voorhees Township, New Jersey, 08043, United States
Clinical Research Alliance
Lake Success, New York, 11042, United States
Memorial Sloan Kettering Cancer Center Dept. of MSKCC
New York, New York, 10065, United States
SUNY - Upstate Medical University Div. of Hematology-Oncology
Syracuse, New York, 13210, United States
University of North Carolina Dept. of LinbergerCancerCtr(3)
Chapel Hill, North Carolina, 27599-7295, United States
Levine Cancer Institute Oncology
Charlotte, North Carolina, 28203, United States
Duke University Medical Center Duke
Durham, North Carolina, 27710, United States
University of Oklahoma Health Sciences Center Dept of OHSC
Oklahoma City, Oklahoma, 73104, United States
St. Luke's Hospital and Health Network St Luke's Hospital (2)
Bethlehem, Pennsylvania, 18015, United States
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, 38120, United States
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
Fort Worth, Texas, 76104, United States
East Texas Medical Center Cancer Institute
Tyler, Texas, 75701, United States
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, 84106, United States
Aurora Advanced Healthcare SC
Milwaukee, Wisconsin, 53215, United States
Novartis Investigative Site
Caba, Buenos Aires, C1405BCH, Argentina
Novartis Investigative Site
La Plata, Buenos Aires, B1902CMK, Argentina
Novartis Investigative Site
Rosario, Santa Fe Province, S2002KDS, Argentina
Novartis Investigative Site
San Miguel de Tucumán, Tucumán Province, T4000IAK, Argentina
Novartis Investigative Site
Woodville, South Australia, 5011, Australia
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Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil
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Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
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São Paulo, São Paulo, 05403-000, Brazil
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Calgary, Alberta, T2N 4N2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, V5Z 4E6, Canada
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Victoria, British Columbia, V8R 6V5, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Greenfield Park, Quebec, J4V 2H1, Canada
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Montreal, Quebec, H2X 3J4, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Herlev, DK-2730, Denmark
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Angers, 49055, France
Novartis Investigative Site
Lille, 59020, France
Novartis Investigative Site
Paris, 75015, France
Novartis Investigative Site
Vandoeuvre-Les-Nancy Cede, 54511, France
Novartis Investigative Site
Aschaffenburg, 63739, Germany
Novartis Investigative Site
Berlin, 10098, Germany
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Weiden, 92637, Germany
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Hong Kong, Hong Kong, Hong Kong
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Shatin, New Territories, Hong Kong, Hong Kong
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Arezzo, AR, 52100, Italy
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Modena, MO, 41100, Italy
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Napoli, 80132, Italy
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Chihuahua City, Chihuahua, 31000, Mexico
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Maastricht, 6229 HX, Netherlands
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The Hague, 2545 CH, Netherlands
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Jesus Maria, Lima region, 11, Peru
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Seoul, Korea, 03080, South Korea
Novartis Investigative Site
Seoul, Korea, 03722, South Korea
Novartis Investigative Site
Seoul, Korea, 05505, South Korea
Novartis Investigative Site
Daejeon, 301-747, South Korea
Novartis Investigative Site
Elche, Alicante, 03203, Spain
Novartis Investigative Site
Seville, Andalusia, 41013, Spain
Novartis Investigative Site
Sabadell, Barcelona, 08208, Spain
Novartis Investigative Site
Lleida, Catalonia, 25198, Spain
Novartis Investigative Site
Niaosong Township, Taiwan, 83301, Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, 112, Taiwan
Novartis Investigative Site
Bangkok, 10700, Thailand
Novartis Investigative Site
Istanbul, 34093, Turkey (Türkiye)
Novartis Investigative Site
Bristol, Avon, BS2 8ED, United Kingdom
Novartis Investigative Site
London, SW3 6JJ, United Kingdom
Novartis Investigative Site
Nottingham, NG5 1PB, United Kingdom
Related Publications (4)
Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.
PMID: 37146227DERIVEDVoss MH, Chen D, Reising A, Marker M, Shi J, Xu J, Ostrovnaya I, Seshan VE, Redzematovic A, Chen YB, Patel P, Han X, Hsieh JJ, Hakimi AA, Motzer RJ. PTEN Expression, Not Mutation Status in TSC1, TSC2, or mTOR, Correlates with the Outcome on Everolimus in Patients with Renal Cell Carcinoma Treated on the Randomized RECORD-3 Trial. Clin Cancer Res. 2019 Jan 15;25(2):506-514. doi: 10.1158/1078-0432.CCR-18-1833. Epub 2018 Oct 16.
PMID: 30327302DERIVEDKnox JJ, Barrios CH, Kim TM, Cosgriff T, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page RD, Beck JT, Cheung F, Yadav S, Patel P, Geoffrois L, Niolat J, Berkowitz N, Marker M, Chen D, Motzer RJ. Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. Ann Oncol. 2017 Jun 1;28(6):1339-1345. doi: 10.1093/annonc/mdx075.
PMID: 28327953DERIVEDMotzer RJ, Barrios CH, Kim TM, Falcon S, Cosgriff T, Harker WG, Srimuninnimit V, Pittman K, Sabbatini R, Rha SY, Flaig TW, Page R, Bavbek S, Beck JT, Patel P, Cheung FY, Yadav S, Schiff EM, Wang X, Niolat J, Sellami D, Anak O, Knox JJ. Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol. 2014 Sep 1;32(25):2765-72. doi: 10.1200/JCO.2013.54.6911. Epub 2014 Jul 21.
PMID: 25049330DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
PRO Tools - completed on Days 1 \& 28 of a cycle. Assessments on D1 coincided with end of a 14-day break for patients on sunitinib but not everolimus. So D1 assessments of patients in sunitinib arm may be less impacted by potential toxicity effects.
Results Point of Contact
- Title
- Study Director
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 24, 2009
First Posted
May 18, 2009
Study Start
October 1, 2009
Primary Completion
May 1, 2015
Study Completion
May 1, 2015
Last Updated
November 8, 2016
Results First Posted
June 28, 2016
Record last verified: 2016-10