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)

• ClinicalTrials.gov Identifier: NCT00903175
• Recruitment Status: Completed
• First Posted: May 18, 2009
• Results First Posted: June 28, 2016
• Last Update Posted: November 8, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Drug: everolimus; Drug: sunitinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 471 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Study Start Date: October 2009
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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)	Drug: 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.; Other Name: RAD001; Drug: 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.
Active Comparator: 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	Drug: 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.; Other Name: RAD001; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival First-Line (PFS 1-L) [ Time Frame: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months ]
   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.

Secondary Outcome Measures :

1. Progression-free Survival Combined (PFS-C) [ Time Frame: 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 ]
   PFS-C (1L and 2L study drugs combined) was a composite endpoint which combined both lines of study treatment. It was defined as the time from the date of randomization to the first of the following: date of death due to any cause, or date of the first radiologically documented progression disease during or after the second-line treatment period for patients with a radiologically documented progression disease in the first-line treatment period and who had crossed-over to second-line treatment no more than 6 weeks after progression.
2. Overall Survival (OS) [ Time Frame: Every 2 months from randomization up to 3 years after last patient randomized ]
   Overall survival was defined as the time from date of randomization to date of death due to any cause. The analysis of OS included all deaths in the FAS regardless of when they were observed.
3. Overall Response Rate (ORR) - First -Line (1-L) [ Time Frame: based on radiological assessments every 3 months until disease progression, start of another antineoplastic therapy or for any other reason up to 35 months ]
   ORR was defined as the number of participants with best overall response (BOR) of complete response (CR) or partial response (PR) and was based on investigator assessment of radiology data per RECIST. Participants with best overall response of 'Unknown' were treated as non-responders in the calculation of the ORR. Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. Radiological assessments : every 12 weeks until disease progression, the start of another antineoplastic therapy or for any other reason.
4. Duration of Response (DoR) - First-Line (1-L) [ Time Frame: 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 overall response (CR or PR) applies only to patients whose Best Overall Response (BOR) was Complete Response (CR) or Partial Response (PR) during the first-line treatment period. The start date was the date of first documented response (CR or PR) during the first-line treatment and the end date was the date of the event defined as the first documented progression or death due to underlying cancer during or after the same treatment line.
5. Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug [ Time Frame: <=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 ]
   The Functional Assessment of Cancer Therapy - Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L of treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.
6. Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined [ Time Frame: <=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 ]
   The Functional Assessment of Cancer Therapy - Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) is a set of items to assess symptoms experienced by patients with advanced kidney cancer. These symptoms include fatigue, pain, weight loss, dyspnea, cough, fever and hematuria. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration was defined as a decrease by at least 3 units compared to baseline, with no later increase above this threshold observed during the 1-L or 2-L treatment. A single measure reporting a decrease of at least 3 units was considered definitive only if it was the last one available for the patient.
7. Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug [ Time Frame: <=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 ]
   The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
8. Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined [ Time Frame: <=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 ]
   The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
9. Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug [ Time Frame: <=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 ]
   The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
10. Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined [ Time Frame: <=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 ]
    The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
11. Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug [ Time Frame: <=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 ]
    The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items.The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line of treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.
12. Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined [ Time Frame: <=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 ]
    The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) contains 30 items. These include a global health status/QoL scale, five functional scales, three symptom scales, and six single items. The standardized score for the PF, fatigue subscales and global health status ranges from 0 to 100, with a higher score representing a high level of functioning/high level of symptom/high quality of life. Definitive deterioration by at least 10% was defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the first line or second line treatment. A single measure reporting a decrease of at least 10% was considered definitive only if it was the last one available for the participant.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients with advanced renal cell carcinoma.
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:

1. Less than 4 weeks post-major surgery
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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)

Birmingham, Alabama, United States, 35294-0006

University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.

Mobile, Alabama, United States, 36688

United States, Arkansas

Highlands Oncology Group HighlandsOncGrp-Bentonville(2)

Fayetteville, Arkansas, United States, 72703

United States, California

University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)

La Jolla, California, United States, 92093-0658

University of California at Los Angeles Dept. of UCLA (3)

Los Angeles, California, United States, 90095

United States, Colorado

University of Colorado Dept. of Anschutz Cancer (2)

Aurora, Colorado, United States, 80045

United States, Connecticut

Norwalk Hospital Norwlak SC

Norwalk, Connecticut, United States, 06856

United States, District of Columbia

Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2

Washington, District of Columbia, United States, 20007-2197

United States, Florida

Lynn Cancer Institute

Boca Raton, Florida, United States, 33486

University of Miami SC

Miami, Florida, United States, 33136

MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando

Orlando, Florida, United States, 32806

United States, Georgia

University Cancer & Blood Center, LLC Dept of NE GCC (2)

Athens, Georgia, United States, 30607

Georgia Health Sciences University Dept. of MCG

Augusta, Georgia, United States, 30912

Summit Cancer Care

Savannah, Georgia, United States, 31405

United States, Illinois

NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital

Chicago, Illinois, United States, 60611

Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)

Maywood, Illinois, United States, 60153

United States, Louisiana

Crescent City Research Consortium, LLC SC

Metairie, Louisiana, United States, 70006

United States, Maryland

VA Maryland Health Care Dept.of GreenbaumCancerCent(7)

Baltimore, Maryland, United States, 21201

Weinberg Cancer Institute at Franklin Square Hospital

Baltimore, Maryland, United States, 21237-3998

United States, Montana

Billings Clinic Dept of Billings Clinic(2)

Billings, Montana, United States, 59107

United States, New Jersey

Hackensack University Medical Center DeptofHackensackUniv.MedCtr.

Hackensack, New Jersey, United States, 07601

Cooper Cancer Center

Voorhees, New Jersey, United States, 08043

United States, New York

Clinical Research Alliance

Lake Success, New York, United States, 11042

Memorial Sloan Kettering Cancer Center Dept. of MSKCC

NY, New York, United States, 10065

SUNY - Upstate Medical University Div. of Hematology-Oncology

Syracuse, New York, United States, 13210

United States, North Carolina

University of North Carolina Dept. of LinbergerCancerCtr(3)

Chapel Hill, North Carolina, United States, 27599-7295

Levine Cancer Institute Oncology

Charlotte, North Carolina, United States, 28203

Duke University Medical Center Duke

Durham, North Carolina, United States, 27710

United States, Oklahoma

University of Oklahoma Health Sciences Center Dept of OHSC

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

St. Luke's Hospital and Health Network St Luke's Hospital (2)

Bethlehem, Pennsylvania, United States, 18015

United States, Tennessee

The West Clinic Dept. of the West Clinic

Memphis, Tennessee, United States, 38120

United States, Texas

The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)

Fort Worth, Texas, United States, 76104

East Texas Medical Center Cancer Institute

Tyler, Texas, United States, 75701

United States, Utah

Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)

Salt Lake City, Utah, United States, 84106

United States, Wisconsin

Aurora Advanced Healthcare SC

Milwaukee, Wisconsin, United States, 53215

Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina, C1405BCH

Novartis Investigative Site

La Plata, Buenos Aires, Argentina, B1902CMK

Novartis Investigative Site

Rosario, Santa Fe, Argentina, S2002KDS

Novartis Investigative Site

Tucuman, Argentina, T4000IAK

Australia, South Australia

Novartis Investigative Site

Woodville, South Australia, Australia, 5011

Brazil

Novartis Investigative Site

Rio de Janeiro, RJ, Brazil, 20230-130

Novartis Investigative Site

Porto Alegre, RS, Brazil, 90610-000

Novartis Investigative Site

Sao Paulo, SP, Brazil, 05403-000

Canada, Alberta

Novartis Investigative Site

Calgary, Alberta, Canada, T2N 4N2

Novartis Investigative Site

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

Novartis Investigative Site

Vancouver, British Columbia, Canada, V5Z 4E6

Novartis Investigative Site

Victoria, British Columbia, Canada, V8R 6V5

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M4N 3M5

Novartis Investigative Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Novartis Investigative Site

Greenfield Park, Quebec, Canada, J4V 2H1

Novartis Investigative Site

Montreal, Quebec, Canada, H2X 3J4

Canada, Saskatchewan

Novartis Investigative Site

Saskatoon, Saskatchewan, Canada, S7N 4H4

Denmark

Novartis Investigative Site

Herlev, Denmark, DK-2730

France

Novartis Investigative Site

Angers cedex 02, France, 49055

Novartis Investigative Site

Lille Cedex, France, 59020

Novartis Investigative Site

Paris, France, 75015

Novartis Investigative Site

Vandoeuvre-Les-Nancy Cede, France, 54511

Germany

Novartis Investigative Site

Aschaffenburg, Germany, 63739

Novartis Investigative Site

Berlin, Germany, 10098

Novartis Investigative Site

Weiden, Germany, 92637

Hong Kong

Novartis Investigative Site

Hongkong, Hong Kong

Novartis Investigative Site

Shatin, New Territories, Hong Kong

Italy

Novartis Investigative Site

Arezzo, AR, Italy, 52100

Novartis Investigative Site

Modena, MO, Italy, 41100

Novartis Investigative Site

Napoli, Italy, 80132

Korea, Republic of

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 03080

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 03722

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 05505

Novartis Investigative Site

Daejeon, Korea, Republic of, 301-747

Mexico

Novartis Investigative Site

Chihuahua, Mexico, 31000

Netherlands

Novartis Investigative Site

Den Haag, Netherlands, 2545 CH

Novartis Investigative Site

Maastricht, Netherlands, 6229 HX

Peru

Novartis Investigative Site

Jesus Maria, Lima, Peru, 11

Spain

Novartis Investigative Site

Elche, Alicante, Spain, 03203

Novartis Investigative Site

Sevilla, Andalucia, Spain, 41013

Novartis Investigative Site

Sabadell, Barcelona, Spain, 08208

Novartis Investigative Site

Lleida, Cataluna, Spain, 25198

Taiwan

Novartis Investigative Site

Taipei, Taiwan, ROC, Taiwan, 112

Novartis Investigative Site

Niaosong Township, Taiwan, 83301

Thailand

Novartis Investigative Site

Bangkok, Thailand, 10700

Turkey

Novartis Investigative Site

Istanbul, Turkey, 34093

United Kingdom

Novartis Investigative Site

Bristol, Avon, United Kingdom, BS2 8ED

Novartis Investigative Site

London, United Kingdom, SW3 6JJ

Novartis Investigative Site

Nottingham, United Kingdom, NG5 1PB

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum in: Ann Oncol. 2018 Nov 1;29(11):2269.

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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00903175
• Other Study ID Numbers: CRAD001L2202; 2009-011056-21 ( EudraCT Number )
• First Posted: May 18, 2009
• Results First Posted: June 28, 2016
• Last Update Posted: November 8, 2016
• Last Verified: October 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

RAD001; everolimus; sunitinib; renal cell carcinoma; kidney cancer; metastatic renal cell cancer; advanced kidney cancer

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Everolimus; Sunitinib; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action