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.

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.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: everolimus; Drug: sunitinib

• Study Type: Interventional
• Enrollment (Actual): 471
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Tucuman, Argentina, T4000IAK
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1405BCH
      • Novartis Investigative Site
    • La Plata, Buenos Aires, Argentina, B1902CMK
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2002KDS
      • Novartis Investigative Site
• Australia
  • South Australia
    • Woodville, South Australia, Australia, 5011
      • Novartis Investigative Site
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20230-130
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 05403-000
      • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Novartis Investigative Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
    • Victoria, British Columbia, Canada, V8R 6V5
      • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2X 3J4
      • Novartis Investigative Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Novartis Investigative Site
• Denmark
  • Herlev, Denmark, DK-2730
    • Novartis Investigative Site
• France
  • 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
    • Novartis Investigative Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Weiden, Germany, 92637
    • Novartis Investigative Site
• Hong Kong
  • Hongkong, Hong Kong
    • Novartis Investigative Site
  • Shatin, New Territories, Hong Kong
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80132
    • Novartis Investigative Site
  • AR
    • Arezzo, AR, Italy, 52100
      • Novartis Investigative Site
  • MO
    • Modena, MO, Italy, 41100
      • Novartis Investigative Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 301-747
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03722
      • Novartis Investigative Site
• Mexico
  • Chihuahua, Mexico, 31000
    • Novartis Investigative Site
• Netherlands
  • Den Haag, Netherlands, 2545 CH
    • Novartis Investigative Site
  • Maastricht, Netherlands, 6229 HX
    • Novartis Investigative Site
• Peru
  • Lima
    • Jesus Maria, Lima, Peru, 11
      • Novartis Investigative Site
• Spain
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Barcelona
    • Sabadell, Barcelona, Spain, 08208
      • Novartis Investigative Site
  • Cataluna
    • Lleida, Cataluna, Spain, 25198
      • Novartis Investigative Site
• Taiwan
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taiwan, ROC
    • Taipei, Taiwan, ROC, Taiwan, 112
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• Turkey
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Novartis Investigative Site
  • Nottingham, United Kingdom, NG5 1PB
    • Novartis Investigative Site
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8ED
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0006
      • University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)
    • Mobile, Alabama, United States, 36688
      • University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group HighlandsOncGrp-Bentonville(2)
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
    • Los Angeles, California, United States, 90095
      • University of California at Los Angeles Dept. of UCLA (3)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Dept. of Anschutz Cancer (2)
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital Norwlak SC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007-2197
      • Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Lynn Cancer Institute
    • Miami, Florida, United States, 33136
      • University of Miami SC
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC Dept of NE GCC (2)
    • Augusta, Georgia, United States, 30912
      • Georgia Health Sciences University Dept. of MCG
    • Savannah, Georgia, United States, 31405
      • Summit Cancer Care
  • Illinois
    • Chicago, Illinois, United States, 60611
      • NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Research Consortium, LLC SC
  • Maryland
    • Baltimore, Maryland, United States, 21237-3998
      • Weinberg Cancer Institute at Franklin Square Hospital
    • Baltimore, Maryland, United States, 21201
      • VA Maryland Health Care Dept.of GreenbaumCancerCent(7)
  • Montana
    • Billings, Montana, United States, 59107
      • Billings Clinic Dept of Billings Clinic(2)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center DeptofHackensackUniv.MedCtr.
    • Voorhees, New Jersey, United States, 08043
      • Cooper Cancer Center
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
    • NY, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center Dept. of MSKCC
    • Syracuse, New York, United States, 13210
      • SUNY - Upstate Medical University Div. of Hematology-Oncology
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • University of North Carolina Dept. of LinbergerCancerCtr(3)
    • Charlotte, North Carolina, United States, 28203
      • Levine Cancer Institute Oncology
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Duke
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center Dept of OHSC
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital and Health Network St Luke's Hospital (2)
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • The West Clinic Dept. of the West Clinic
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
    • Tyler, Texas, United States, 75701
      • East Texas Medical Center Cancer Institute
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Advanced Healthcare SC

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Combined (PFS-C)	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.	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)	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.	Every 2 months from randomization up to 3 years after last patient randomized
Overall Response Rate (ORR) - First -Line (1-L)	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.	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)	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.	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	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.	<=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
Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined	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.	<=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
Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug	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.	<=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
Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined	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.	<=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
Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug	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.	<=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
Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined	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.	<=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
Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug	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.	<=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
Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined	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.	<=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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: April 24, 2009
• First Submitted That Met QC Criteria: May 14, 2009
• First Posted (Estimate): May 18, 2009

Study Record Updates

• Last Update Posted (Estimate): November 8, 2016
• Last Update Submitted That Met QC Criteria: October 4, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: sunitinib; kidney cancer; everolimus; renal cell carcinoma; RAD001; metastatic renal cell cancer; advanced kidney cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Sunitinib; Everolimus
• Other Study ID Numbers: CRAD001L2202; 2009-011056-21 (EudraCT Number)