Renal Cell CarcinomaPhase 2RECORD-3NCT00903175
Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma
A Phase 2 study testing everolimus and sunitinib in people with Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 84 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- everolimus and sunitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 471 participants
- Where
- 84 sitesin 19 countries
- Study dates
- Oct 2009to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 37Show fewer
- 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
- 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.
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥160mmHg or diastolic blood pressure (DBP) of ≥ 95mmHg]
- Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent
- Patients with a known history of HIV seropositivity.
- Patients with active bleeding.
- 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.
- History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).
- 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.
- Patients who have a history of another primary malignancy and off treatment for ≤ 3 years
- Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.
- Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start.
- Patients unwilling or unable to comply with the protocol.
Trial locations and contacts
84 sites in 19 countries.
84 sites in 19 countries
United States35 sites
University Cancer & Blood Center, LLC Dept of NE GCC (2)
Athens, Georgia, 30607
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, 30912
University of Colorado Dept. of Anschutz Cancer (2)
Aurora, Colorado, 80045
VA Maryland Health Care Dept.of GreenbaumCancerCent(7)
Baltimore, Maryland, 21201
Weinberg Cancer Institute at Franklin Square Hospital
Baltimore, Maryland, 21237-3998
St. Luke's Hospital and Health Network St Luke's Hospital (2)
Bethlehem, Pennsylvania, 18015
Billings Clinic Dept of Billings Clinic(2)
Billings, Montana, 59107
University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)
Birmingham, Alabama, 35294-0006
Lynn Cancer Institute
Boca Raton, Florida, 33486
University of North Carolina Dept. of LinbergerCancerCtr(3)
Chapel Hill, North Carolina, 27599-7295
Levine Cancer Institute Oncology
Charlotte, North Carolina, 28203
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital
Chicago, Illinois, 60611
Duke University Medical Center Duke
Durham, North Carolina, 27710
Highlands Oncology Group HighlandsOncGrp-Bentonville(2)
Fayetteville, Arkansas, 72703
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
Fort Worth, Texas, 76104
Hackensack University Medical Center DeptofHackensackUniv.MedCtr.
Hackensack, New Jersey, 07601
University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)
La Jolla, California, 92093-0658
Clinical Research Alliance
Lake Success, New York, 11042
University of California at Los Angeles Dept. of UCLA (3)
Los Angeles, California, 90095
Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)
Maywood, Illinois, 60153
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, 38120
Crescent City Research Consortium, LLC SC
Metairie, Louisiana, 70006
University of Miami SC
Miami, Florida, 33136
Aurora Advanced Healthcare SC
Milwaukee, Wisconsin, 53215
University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
Mobile, Alabama, 36688
Memorial Sloan Kettering Cancer Center Dept. of MSKCC
New York, New York, 10065
Norwalk Hospital Norwlak SC
Norwalk, Connecticut, 06856
University of Oklahoma Health Sciences Center Dept of OHSC
Oklahoma City, Oklahoma, 73104
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando
Orlando, Florida, 32806
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, 84106
Summit Cancer Care
Savannah, Georgia, 31405
SUNY - Upstate Medical University Div. of Hematology-Oncology
Syracuse, New York, 13210
East Texas Medical Center Cancer Institute
Tyler, Texas, 75701
Cooper Cancer Center
Voorhees Township, New Jersey, 08043
Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2
Washington D.C., District of Columbia, 20007-2197
Canada9 sites
Novartis Investigative Site
Calgary, Alberta, T2N 4N2
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Greenfield Park, Quebec, J4V 2H1
Novartis Investigative Site
Montreal, Quebec, H2X 3J4
Novartis Investigative Site
Saskatoon, Saskatchewan, S7N 4H4
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Novartis Investigative Site
Vancouver, British Columbia, V5Z 4E6
Novartis Investigative Site
Victoria, British Columbia, V8R 6V5
Argentina4 sites
Novartis Investigative Site
Caba, Buenos Aires, C1405BCH
Novartis Investigative Site
La Plata, Buenos Aires, B1902CMK
Novartis Investigative Site
Rosario, Santa Fe Province, S2002KDS
Novartis Investigative Site
San Miguel de Tucumán, Tucumán Province, T4000IAK
France4 sites
Novartis Investigative Site
Angers, 49055
Novartis Investigative Site
Lille, 59020
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Vandoeuvre-Les-Nancy Cede, 54511
South Korea4 sites
Novartis Investigative Site
Daejeon, 301-747
Novartis Investigative Site
Seoul, Korea, 03080
Novartis Investigative Site
Seoul, Korea, 03722
Novartis Investigative Site
Seoul, Korea, 05505
Spain4 sites
Novartis Investigative Site
Elche, Alicante, 03203
Novartis Investigative Site
Lleida, Catalonia, 25198
Novartis Investigative Site
Sabadell, Barcelona, 08208
Novartis Investigative Site
Seville, Andalusia, 41013
Brazil3 sites
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90610-000
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20230-130
Novartis Investigative Site
São Paulo, São Paulo, 05403-000
Germany3 sites
Novartis Investigative Site
Aschaffenburg, 63739
Novartis Investigative Site
Berlin, 10098
Novartis Investigative Site
Weiden, 92637
Italy3 sites
Novartis Investigative Site
Arezzo, AR, 52100
Novartis Investigative Site
Modena, MO, 41100
Novartis Investigative Site
Naples, 80132
United Kingdom3 sites
Novartis Investigative Site
Bristol, Avon, BS2 8ED
Novartis Investigative Site
London, SW3 6JJ
Novartis Investigative Site
Nottingham, NG5 1PB
Hong Kong2 sites
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Shatin, New Territories, Hong Kong
Netherlands2 sites
Novartis Investigative Site
Maastricht, 6229 HX
Novartis Investigative Site
The Hague, 2545 CH
Taiwan2 sites
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
Novartis Investigative Site
Taipei, Taiwan, ROC, 112
Australia1 site
Novartis Investigative Site
Woodville, South Australia, 5011
About this study
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.
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.
- Conditions
- Renal Cell Carcinoma
- Being tested
- everolimus, sunitinib
- Keywords
- RAD001, everolimus, sunitinib, renal cell carcinoma, kidney cancer, metastatic renal cell cancer, advanced kidney cancer
- Medical subject headings
- Carcinoma, Renal Cell, Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called RAD001
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.
sunitinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| everolimus 1L/sunitinib 2L | Experimental | 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) Receives: Drug: everolimus; Drug: sunitinib |
| sunitinib 1L/everolimus 2L | Active comparator | 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 Receives: Drug: everolimus; Drug: sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: <=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.
Measured: <=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.
Measured: <=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.
Measured: <=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.
Measured: <=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.
Measured: <=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.
Measured: <=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.
Measured: <=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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 471 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903175
- Sponsor's protocol ID
- CRAD001L2202
- Other IDs
- 2009-011056-21, 2009
- Acronym
- RECORD-3
- Status last verified
- Oct 2016
- First submitted
- 24 Apr 2009
- Last updated
- 8 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 37146227Voss 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.
PubMed 30327302Knox 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.
PubMed 28327953Motzer 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.
PubMed 25049330
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00903175
- Acronym / sponsor ID
- RECORD-3 / CRAD001L2202
- Conditions
- Renal Cell Carcinoma
- Keywords
- RAD001, everolimus, sunitinib, renal cell carcinoma, kidney cancer, metastatic renal cell cancer, advanced kidney cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 471 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 18 May 2009 (estimated)
- Results
- Posted 28 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| everolimus 1L/sunitinib 2L | Experimental | Drug: everolimus, Drug: sunitinibeverolimus 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 comparator | Drug: everolimus, Drug: sunitinibsunitinib 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (37 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: RAD001Everolimus 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. | Drug | everolimus 1L/sunitinib 2L, sunitinib 1L/everolimus 2L |
| sunitinibSunitinib 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. | Drug | everolimus 1L/sunitinib 2L, sunitinib 1L/everolimus 2L |
Primary outcome
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.
12 secondary outcomes
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
Overall Survival (OS)
Time frame: Every 2 months from randomization up to 3 years after last patient randomized
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
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
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
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
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
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37146227Aldin 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.
- Derived from this study: PubMed 30327302Voss 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.
- Derived from this study: PubMed 28327953Knox 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.
- Derived from this study: PubMed 25049330Motzer 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 InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
84 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus and sunitinib in people with Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 84 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in United States, Canada, Argentina, France, South Korea and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00903175, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2016.