Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma
NCT ID: NCT00903175
Last Updated: 2016-11-08
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
471 participants
INTERVENTIONAL
2009-10-31
2015-05-31
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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everolimus 1L/sunitinib 2L
everolimus 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)
everolimus
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
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.
sunitinib 1L/everolimus 2L
sunitinib 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
everolimus
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
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.
Interventions
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everolimus
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
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patients with at least one measurable lesion.
3. Patients with a Karnofsky Performance Status ≥70%.
4. Adequate bone marrow function.
5. Adequate liver function.
6. Adequate renal function.
7. Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN)
8. 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.
Exclusion Criteria
2. 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).
3. Patients in need for major surgical procedure during the course of the study
4. Patients with a serious non-healing wound, ulcer, or bone fracture
5. Patients with a history of seizure(s) not controlled with standard medical therapy
6. Patients who have received prior systemic treatment for their metastatic RCC
7. 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.
8. 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
9. Patients with a known hypersensitivity to sunitinib or its excipients
10. 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)
11. Clinically significant gastrointestinal abnormalities including, but not limited to:
* Malabsorption syndrome
* Major resection of the stomach or small bowel that could affect the absorption of study drug
* Active peptic ulcer disease
* Inflammatory bowel disease
* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation
* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
12. Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg\]
13. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
14. Patients with a known history of HIV seropositivity.
15. Patients with active bleeding.
16. Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as:
* Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction ≤ 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents ≤ 6 months before study treatment start.
* Prolongation of corrected QT interval (QTc) \> 500 milliseconds (msecs).
* Severally impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 0\^2 saturation that is 88% or less at rest on room air.
* Poorly controlled diabetes as defined by fasting serum glucose \>2.0 x ULN.
* Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.
* Liver disease such as chronic active hepatitis or chronic persistent hepatitis.
17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
18. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.
19. Patients who have a history of another primary malignancy and off treatment for ≤ 3 years
20. Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.
21. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
22. Patients unwilling or unable to comply with the protocol.
18 Years
ALL
No
Sponsors
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Novartis Pharmaceuticals
INDUSTRY
Responsible Party
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Principal Investigators
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Novartis Pharmaceuticals
Role: STUDY_DIRECTOR
Novartis Pharmaceuticals
Locations
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University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)
Birmingham, Alabama, United States
University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
Mobile, Alabama, United States
Highlands Oncology Group HighlandsOncGrp-Bentonville(2)
Fayetteville, Arkansas, United States
University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
La Jolla, California, United States
University of California at Los Angeles Dept. of UCLA (3)
Los Angeles, California, United States
University of Colorado Dept. of Anschutz Cancer (2)
Aurora, Colorado, United States
Norwalk Hospital Norwlak SC
Norwalk, Connecticut, United States
Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2
Washington D.C., District of Columbia, United States
Lynn Cancer Institute
Boca Raton, Florida, United States
University of Miami SC
Miami, Florida, United States
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando
Orlando, Florida, United States
University Cancer & Blood Center, LLC Dept of NE GCC (2)
Athens, Georgia, United States
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, United States
Summit Cancer Care
Savannah, Georgia, United States
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital
Chicago, Illinois, United States
Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)
Maywood, Illinois, United States
Crescent City Research Consortium, LLC SC
Metairie, Louisiana, United States
VA Maryland Health Care Dept.of GreenbaumCancerCent(7)
Baltimore, Maryland, United States
Weinberg Cancer Institute at Franklin Square Hospital
Baltimore, Maryland, United States
Billings Clinic Dept of Billings Clinic(2)
Billings, Montana, United States
Hackensack University Medical Center DeptofHackensackUniv.MedCtr.
Hackensack, New Jersey, United States
Cooper Cancer Center
Voorhees Township, New Jersey, United States
Clinical Research Alliance
Lake Success, New York, United States
Memorial Sloan Kettering Cancer Center Dept. of MSKCC
New York, New York, United States
SUNY - Upstate Medical University Div. of Hematology-Oncology
Syracuse, New York, United States
University of North Carolina Dept. of LinbergerCancerCtr(3)
Chapel Hill, North Carolina, United States
Levine Cancer Institute Oncology
Charlotte, North Carolina, United States
Duke University Medical Center Duke
Durham, North Carolina, United States
University of Oklahoma Health Sciences Center Dept of OHSC
Oklahoma City, Oklahoma, United States
St. Luke's Hospital and Health Network St Luke's Hospital (2)
Bethlehem, Pennsylvania, United States
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, United States
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
Fort Worth, Texas, United States
East Texas Medical Center Cancer Institute
Tyler, Texas, United States
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, United States
Aurora Advanced Healthcare SC
Milwaukee, Wisconsin, United States
Novartis Investigative Site
Caba, Buenos Aires, Argentina
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La Plata, Buenos Aires, Argentina
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Rosario, Santa Fe Province, Argentina
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San Miguel de Tucumán, Tucumán Province, Argentina
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Woodville, South Australia, Australia
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Rio de Janeiro, Rio de Janeiro, Brazil
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Porto Alegre, Rio Grande do Sul, Brazil
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São Paulo, São Paulo, Brazil
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Vancouver, British Columbia, Canada
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Victoria, British Columbia, Canada
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Toronto, Ontario, Canada
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Toronto, Ontario, Canada
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Greenfield Park, Quebec, Canada
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Montreal, Quebec, Canada
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Saskatoon, Saskatchewan, Canada
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Herlev, , Denmark
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Angers, , France
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Lille, , France
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Paris, , France
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Vandoeuvre-Les-Nancy Cede, , France
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Aschaffenburg, , Germany
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Berlin, , Germany
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Weiden, , 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, Italy
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Modena, MO, Italy
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Napoli, , Italy
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Chihuahua City, Chihuahua, Mexico
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Maastricht, , Netherlands
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The Hague, , Netherlands
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Jesus Maria, Lima region, Peru
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Seoul, Korea, South Korea
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Seoul, Korea, South Korea
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Seoul, Korea, South Korea
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Daejeon, , South Korea
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Elche, Alicante, Spain
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Seville, Andalusia, Spain
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Sabadell, Barcelona, Spain
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Lleida, Catalonia, Spain
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Niaosong Township, Taiwan, Taiwan
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Taipei, Taiwan, ROC, Taiwan
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Bangkok, , Thailand
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Istanbul, , Turkey (Türkiye)
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Bristol, Avon, United Kingdom
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London, , United Kingdom
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Nottingham, , United Kingdom
Countries
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References
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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.
Voss 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.
Knox 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.
Motzer 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.
Related Links
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Related Info
Other Identifiers
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2009-011056-21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CRAD001L2202
Identifier Type: -
Identifier Source: org_study_id