Metastatic Renal Cell CarcinomaPhase 3RECORD-1NCT00410124
RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
A Phase 3 study testing RAD001 in people with Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 93 sites in 10 countries.
Trial summary
To assess whether daily treatment with RAD001 could slow the growth and spread of metastatic carcinoma of the kidney. The safety of RAD001 was also to be studied in this trial. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Metastatic Renal Cell Carcinoma
- What is being tested?
- RAD001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 416 participants
- Where
- 93 sitesin 10 countries
- Study dates
- Nov 2006to Oct 2011
- Phase
- Phase 3
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable).
- The date of progression on sunitinib and/or sorafenib must be within 6 months.
- Patients may have received one or both agents
- Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted.
- Prior vaccine therapy in the adjuvant setting is permitted.
- Patients with at least one measurable lesion at baseline as per the Response evaluation criteria in solid tumors (RECIST) criteria, either on physical exam or as determined by Computer Tomography (CT) Scan or Magnetic Resonance Imaging (MRI).
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- Patients with a Karnofsky Performance Status ≥70%.
- Adequate bone marrow, liver and renal function.
- Patients with a life expectancy ≥ 3 months.
- Women of childbearing potential must have had a negative serum or urine pregnancy test 48 hours prior to the administration of the first study treatment.
- Patients who give a written informed consent obtained according to local guidelines
Who cannot join
- Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these within 4 weeks of study entry
- Patients who have previously received mTOR inhibitors.
- Patients with a known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Patients with untreated CNS metastases or who are neurologically unstable despite treatment of the CNS metastases. (Patients with treated CNS metastases, who are neurologically stable off of corticosteroids, are eligible to enter study).
- Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
- Patients with a known history of HIV seropositivity.
Show all 13Show fewer
- Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumadin)
- Patients who have any severe and/or uncontrolled medical conditions
- Patients who have a history of another primary malignancy ≤ 3 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes.
- Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to randomization
- Patients unwilling to or unable to comply with the protocol
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
93 sites in 10 countries.
93 sites in 10 countries
United States31 sites
Novartis Investigative Site
Baltimore, Maryland, 21201
Novartis Investigative Site
Bedford, Texas, 76022
Novartis Investigative Site
Buffalo, New York, 14263
Novartis Investigative Site
Canton, Ohio, 44718
Novartis Investigative Site
Chapel Hill, North Carolina, 27599
Novartis Investigative Site
Columbia, Missouri, 65201
Novartis Investigative Site
Dallas, Texas, 75246
Novartis Investigative Site
Detroit, Michigan, 48201
Novartis Investigative Site
Duarte, California, 91010-3000
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
Fayetteville, Arkansas, 72703
Novartis Investigative Site
Indianapolis, Indiana, 46202
Novartis Investigative Site
Indianapolis, Indiana, 46227
Novartis Investigative Site
Las Vegas, Nevada, 89135
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Minneapolis, Minnesota, 55455
Novartis Investigative Site
Morgantown, West Virginia, 26506
Novartis Investigative Site
New York, New York, 10021
Novartis Investigative Site
Ocoee, Florida, *see dep*
Novartis Investigative Site
Orlando, Florida, 32806
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15232
Novartis Investigative Site
Portland, Oregon, 97210
Novartis Investigative Site
Raleigh, North Carolina, 27609
Novartis Investigative Site
Sacramento, California, 95817
Novartis Investigative Site
San Antonio, Texas, 78229
Novartis Investigative Site
San Francisco, California, 94115
Novartis Investigative Site
Santa Monica, California, 90404
Novartis Investigative Site
Seattle, Washington, 98109-1023
Novartis Investigative Site
Spokane, Washington, 99202
Novartis Investigative Site
St Louis, Missouri, 63110
Novartis Investigative Site
Tyler, Texas, 75702
Japan14 sites
Novartis Investigative Site
Akita, Akita, 010-8543
Novartis Investigative Site
Chiba, Chiba, 260-8717
Novartis Investigative Site
Chuo-ku, Tokyo, 104-0045
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Kurashiki, Okayama-ken, 710-8602
Novartis Investigative Site
Matsuyama, Ehime, 791-0280
Novartis Investigative Site
Osaka, Osaka, 537-8511
Novartis Investigative Site
Sapporo, Hokkaido, 060-8543
Novartis Investigative Site
Sapporo, Hokkaido, 060-8648
Novartis Investigative Site
Sayama, Osaka, 589-8511
Novartis Investigative Site
Sunto-gun, Shizuoka, 411-8777
Novartis Investigative Site
Tokushima, Tokushima, 770-8503
Novartis Investigative Site
Tsukuba, Ibaraki, 305-8576
Novartis Investigative Site
Utsunomiya, Tochigi, 320-0834
France8 sites
Novartis Investigative Site
Bordeaux, 33075
Novartis Investigative Site
Lille, 59020
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Paris, 75015
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Novartis Investigative Site
Strasbourg, 67091
Novartis Investigative Site
Toulouse, 31052
Novartis Investigative Site
Villejuif, 94805
Italy8 sites
Novartis Investigative Site
Cremona, CR, 26100
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Modena, MO, 41100
Novartis Investigative Site
Naples, 80132
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Perugia, PG, 06129
Novartis Investigative Site
Roma, RM, 00152
Canada7 sites
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Hamilton, Ontario, L8V 5C2
Novartis Investigative Site
London, Ontario, N6A 4G5
Novartis Investigative Site
Montreal, Quebec, H3G 1A4
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Novartis Investigative Site
Vancouver, Alberta, V5Z 4E6
Australia6 sites
Novartis Investigative Site
Camperdown, New South Wales, 2050
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
Randwick, New South Wales, 2031
Novartis Investigative Site
South Brisbane, Queensland, 4101
Novartis Investigative Site
Westmead, New South Wales, 2145
Novartis Investigative Site
Woodville, South Australia, 5011
Germany6 sites
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Frankfurt/M, 60590
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Kassel, 34125
Novartis Investigative Site
Mainz, 55101
Novartis Investigative Site
München, 81675
Spain5 sites
Novartis Investigative Site
Barcelona, Barcelona, 08035
Novartis Investigative Site
Barcelona, Spain, 08025
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Valencia, 46009
Netherlands4 sites
Novartis Investigative Site
Amsterdam
Novartis Investigative Site
Leiden, 2300 RC
Novartis Investigative Site
Nijmegen, 6525 GA
Novartis Investigative Site
Utrecht, Netherlands, 3584CX
Poland4 sites
Novartis Investigative Site
Gdañsk, 80-219
Novartis Investigative Site
Lodz, 90-153
Novartis Investigative Site
Warsaw, 00-909
Novartis Investigative Site
Wroclaw, 50-367
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Compare the Safety and Efficacy of RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed on VEGF Receptor Tyrosine Kinase Inhibitor
To assess whether daily treatment with RAD001 could slow the growth and spread of metastatic carcinoma of the kidney. The safety of RAD001 was also to be studied in this trial.
- Conditions
- Metastatic Renal Cell Carcinoma
- Being tested
- RAD001, Placebo
- Keywords
- advanced kidney cancer, everolimus, kidney cancer, oral therapy
- 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.
RAD001Drug
Also called Everolimus
The dose of RAD001 was 10 mg/day. Patients were instructed to take two tablets (5 mg each) by mouth every day.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| RAD001 +BSC | Experimental | The study drugs were self administered by the patients. Patients were instructed to take the study drug as specified in the protocol. Patients were instructed to take two tablets (5 mg each) by mouth every day. Tablets were to be taken one tablet after another with a glass of water, at the same time each day in a fasting state or with a light fat-free meal. If disease progression occurred, patients were unblinded and if they were receiving RAD001, they would discontinue the study. Otherwise, they would be given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day. Receives: Drug: RAD001 |
| Placebo (plus BSC) | Placebo comparator | Patients received matching placebo of RAD001 tablets twice a day along with Best Supportive Care. With the documented disease progression, the investigator could unblind the patient. If unblinded patient was receiving placebo treatment, they were given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progressive Free Survival (PFS) in Patients Who Receive RAD001 Plus Best Supportive Care(BSC) Versus Patients Who Receive Matching Placebo Plus BSC
Progression Free survival is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary statistical analysis of PFS was based on central radiological assessments using a one-sided stratified log-rank test. Radiological assessments: every 8 weeks (+/-1 week) during the first year and every 12 weeks (+/- 1 week) during the second year and thereafter and at the end of the study. Kaplan-Meier methodology was used to estimate the median PFS for each treatment group.
Measured: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported between date of first patient randomized until 28Feb2008 cut of date.
Secondary outcomes (12)
Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. Kaplan-Meier methodology was used to estimate the median overall survival for each treatment group
Measured: Assessed every month up to 2 years after the last patient was randomized into the study from the date of randomization to the time of death. (Data cutoff was 15Nov2009)
Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC
The Best Overall Response rate (BOR) is defined as the percentage of patients having achieved confirmed Complete Response + Partial Response. Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. • Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Radiological assessments: every 8 weeks (+/-1 week) during the first year and every 12 weeks (+/- 1 week) during the second year and thereafter and at the end of the study.
Measured: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date
Duration of Response in Patients Who Receive RAD001 Plus BSC Versus Placebo Plus BSC
Duration of overall response (CR or PR) applies only to patients whose Best Overall Response (BOR) was Complete Response (CR) or Partial Response (PR). The start date is the date of first documented response (CR or PR) and the end date is the date of event defined as the first documented progression or death. Radiological assessments: every 8 weeks (+/-1 week) during the first year and every 12 weeks (+/- 1 week) during the second year and thereafter and at the end of the study.
Measured: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date
Analysis of Time to Definitive Deterioration of the Global Health Status/QoL Scale(QL) Scores of the EORTC QLQ-30 Questionnaire by at Least 10 Percent Using Kaplan Meier Method, by Treatment.
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. Global health status / QoL scale (QL), consisting of 2 questions each scored from 1 (very poor) to 7 (excellent), and with possible scores ranging from 2 to 14. Higher score indicates better functioning. Definitive deterioration by at least 10% is defined as a decrease in score by at least 10% compared to baseline, with no increase above this threshold observed during the course of the study. A single measure reporting a decrease of at least 10% is considered definitive only if it is the last one available for the patient. Time to definitive deterioration is the number of days between the date of randomization and date of assessment at which definitive deterioration is seen.
Measured: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Time to Definitive Deterioration of the FKS-DRS Risk Score by at Least 2 Score Units Using Kaplan-Meier Method, by Treatment.
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. There were 4 response categories (1=Not at all, 2= A little, 3=Quite a bit, 4=Very much), sum of item responses can range from 0 to 36. "0"= severely symptomatic patient and the highest score is an asymptomatic patient. Definitive deterioration of the FKSI-DRS score was defined as a decrease by at least 2 units compared to baseline, with no later increase above this threshold observed during the study. A single measure reporting a decrease of at least 2 units was considered definitive only if it is the last one available for the patient. Time to definitive deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen.
Measured: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Time to Definitive Deterioration of the Physical Functioning Scale (PF)Score of the EORTC QLQ-C30 Questionnaire by at Least 10 Percent Using Kaplan_Meier Method, by Treatment.
The EORTC QLQ-C30 contains 30 items. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). Physical Functioning (PF) sub-scale, consisting of 5 questions each scored from 1 (not at all) to 4 (very much), and with possible values ranging from 5 to 20. Definitive deterioration by at least 10% is defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. A single measure reporting a decrease of at least 10% is considered definitive only if it is the last one available for the patient. Time to definitive deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen.
Measured: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Pharmacokinetics of RAD001:Peak Concentration in a Dosing Interval (C-max); Pre-dose Concentration at 24-h Time Point in Dosing Interval (C-min) and Average Concentration in a Dosing Interval =(C-avg)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol. C-avg= Area under curve (AUC) in a dosing interval from time-zero to time of the last quantifiable concentration (AUC0-tlast)/ time of the last quantifiable concentration in a dosing interval (tlast)
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day1, Cycle 1 Day 15 and at pre-dose from Cycle 2(day1) and all subsequent treatment cycles up until data cut-off 28 Feb 2008.
Pharmacokinetics of RAD001: Time at Which C-Max Occurs (t-Max)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol.
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose of From Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Area Under Curve (AUC) in a Dosing Interval From Time-zero to Time of the Last Quantifiable Concentration. (AUC 0-tlast)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol.
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Time of the Last Quantifiable Concentration in a Dosing Interval - (Tlast)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol.
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Apparent Systemic Clearance From Blood Following Extravascular Administration (CL/F)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol.Apparent oral clearance of RAD001 (CL/F) was calculated using AUC in a dosing interval of 24 hours (AUC0-24hours) value on Day 15 as: CL/F = dose/ AUC0-τ
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Normalized to Body Surface Area (CL/F)
Blood samples will be collected by direct venipuncture during regularly scheduled visits according to the collection plan provided in the study protocol.
Measured: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2006 (estimated)
- Study startNov 2006
- Primary completionFeb 2008
- Study completionOct 2011
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 (7)Papers the sponsor has linked to this study.
- Other trials for Metastatic 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 416 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
- NCT00410124
- Sponsor's protocol ID
- CRAD001C2240
- Other IDs
- 2006-002070-21
- Acronym
- RECORD-1
- Status last verified
- Dec 2012
- First submitted
- 11 Dec 2006
- Last updated
- 15 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Stein A, Bellmunt J, Escudier B, Kim D, Stergiopoulos SG, Mietlowski W, Motzer RJ; RECORD-1 Trial Study Group. Survival prediction in everolimus-treated patients with metastatic renal cell carcinoma incorporating tumor burden response in the RECORD-1 trial. Eur Urol. 2013 Dec;64(6):994-1002. doi: 10.1016/j.eururo.2012.11.032. Epub 2012 Nov 21.
PubMed 23219086Stein A, Wang W, Carter AA, Chiparus O, Hollaender N, Kim H, Motzer RJ, Sarr C. Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial. BMC Cancer. 2012 Jul 23;12:311. doi: 10.1186/1471-2407-12-311.
PubMed 22824201Oudard S, Thiam R, Fournier LS, Medioni J, Lamuraglia M, Scotte F, Fabre E, Kim D, Kpamegan E, Panneerselvam A, Cuenod CA. Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study. Eur J Cancer. 2012 Jul;48(10):1512-8. doi: 10.1016/j.ejca.2012.01.027. Epub 2012 Feb 16.
PubMed 22342553Porta C, Calvo E, Climent MA, Vaishampayan U, Osanto S, Ravaud A, Bracarda S, Hutson TE, Escudier B, Grunwald V, Kim D, Panneerselvam A, Anak O, Motzer RJ. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol. 2012 Apr;61(4):826-33. doi: 10.1016/j.eururo.2011.12.057. Epub 2012 Jan 5.
PubMed 22297244Calvo E, Escudier B, Motzer RJ, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Ravaud A, Kim D, Panneerselvam A, Anak O, Figlin RA. Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer. 2012 Feb;48(3):333-9. doi: 10.1016/j.ejca.2011.11.027. Epub 2011 Dec 30.
PubMed 22209391White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, Uemura H, Kpamegan E, Kay A, Robson M, Ravaud A, Motzer RJ. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.
PubMed 20194812Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. doi: 10.1016/S0140-6736(08)61039-9. Epub 2008 Jul 22.
PubMed 18653228
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study to Compare the Safety and Efficacy of RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed on VEGF Receptor Tyrosine Kinase Inhibitor
- ClinicalTrials.gov ID
- NCT00410124
- Acronym / sponsor ID
- RECORD-1 / CRAD001C2240
- Conditions
- Metastatic Renal Cell Carcinoma
- Keywords
- advanced kidney cancer, everolimus, kidney cancer, oral therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 416 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Feb 2008 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 12 Dec 2006 (estimated)
- Results
- Posted 15 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess whether daily treatment with RAD001 could slow the growth and spread of metastatic carcinoma of the kidney. The safety of RAD001 was also to be studied in this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RAD001 +BSC | Experimental | Drug: RAD001The study drugs were self administered by the patients. Patients were instructed to take the study drug as specified in the protocol. Patients were instructed to take two tablets (5 mg each) by mouth every day. Tablets were to be taken one tablet after another with a glass of water, at the same time each day in a fasting state or with a light fat-free meal. If disease progression occurred, patients were unblinded and if they were receiving RAD001, they would discontinue the study. Otherwise, they would be given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day. |
| Placebo (plus BSC) | Placebo comparator | Drug: PlaceboPatients received matching placebo of RAD001 tablets twice a day along with Best Supportive Care. With the documented disease progression, the investigator could unblind the patient. If unblinded patient was receiving placebo treatment, they were given the option to continue in the extension open label phase of 2 tablets of RAD001 5mg by mouth every day. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with metastatic carcinoma and with histological or cytological confirmation of clear cell RCC (tissue from the original diagnosis of renal cell cancer is acceptable).
- The date of progression on sunitinib and/or sorafenib must be within 6 months.
- Patients may have received one or both agents
- Prior therapy with cytokines (i.e., IL-2, Interferon) and/or VEGF-ligand inhibitors (i.e., bevacizumab) are permitted.
- Prior vaccine therapy in the adjuvant setting is permitted.
Key exclusion criteria (13 listed)
- Patients currently receiving chemotherapy, immunotherapy, or radio-therapy or who have received these within 4 weeks of study entry
- Patients who have previously received mTOR inhibitors.
- Patients with a known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus) or to its excipients.
- Patients with untreated CNS metastases or who are neurologically unstable despite treatment of the CNS metastases. (Patients with treated CNS metastases, who are neurologically stable off of corticosteroids, are eligible to enter study).
- Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
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 |
|---|---|---|
| RAD001Also: EverolimusThe dose of RAD001 was 10 mg/day. Patients were instructed to take two tablets (5 mg each) by mouth every day. | Drug | RAD001 +BSC |
| Placebo | Drug | Placebo (plus BSC) |
Primary outcome
Progressive Free Survival (PFS) in Patients Who Receive RAD001 Plus Best Supportive Care(BSC) Versus Patients Who Receive Matching Placebo Plus BSC
Time frame: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported between date of first patient randomized until 28Feb2008 cut of date.
Progression Free survival is defined as the time from randomization to the date of first documented disease progression or death from any cause. The primary statistical analysis of PFS was based on central radiological assessments using a one-sided stratified log-rank test. Radiological assessments: every 8 weeks (+/-1 week) during the first year and every 12 weeks (+/- 1 week) during the second year and thereafter and at the end of the study. Kaplan-Meier methodology was used to estimate the median PFS for each treatment group.
12 secondary outcomes
Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments
Time frame: Assessed every month up to 2 years after the last patient was randomized into the study from the date of randomization to the time of death. (Data cutoff was 15Nov2009)
Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC
Time frame: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date
Duration of Response in Patients Who Receive RAD001 Plus BSC Versus Placebo Plus BSC
Time frame: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported, between date of first patient randomized until 28Feb2008 cutoff date
Analysis of Time to Definitive Deterioration of the Global Health Status/QoL Scale(QL) Scores of the EORTC QLQ-30 Questionnaire by at Least 10 Percent Using Kaplan Meier Method, by Treatment.
Time frame: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Time to Definitive Deterioration of the FKS-DRS Risk Score by at Least 2 Score Units Using Kaplan-Meier Method, by Treatment.
Time frame: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Time to Definitive Deterioration of the Physical Functioning Scale (PF)Score of the EORTC QLQ-C30 Questionnaire by at Least 10 Percent Using Kaplan_Meier Method, by Treatment.
Time frame: Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Pharmacokinetics of RAD001:Peak Concentration in a Dosing Interval (C-max); Pre-dose Concentration at 24-h Time Point in Dosing Interval (C-min) and Average Concentration in a Dosing Interval =(C-avg)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day1, Cycle 1 Day 15 and at pre-dose from Cycle 2(day1) and all subsequent treatment cycles up until data cut-off 28 Feb 2008.
Pharmacokinetics of RAD001: Time at Which C-Max Occurs (t-Max)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose of From Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Area Under Curve (AUC) in a Dosing Interval From Time-zero to Time of the Last Quantifiable Concentration. (AUC 0-tlast)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Time of the Last Quantifiable Concentration in a Dosing Interval - (Tlast)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Apparent Systemic Clearance From Blood Following Extravascular Administration (CL/F)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Pharmacokinetics of RAD001: Normalized to Body Surface Area (CL/F)
Time frame: At pre-dose and post-dose: 1 hour, 2 hour, 5 hour, 24 hour of Cycle 1 Day 1, Cycle 1 Day 15 and at pre-dose from Cycle 2 (Day 1) and all subsequent treatment cycles until data cut-off 28Feb2008.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23219086Stein A, Bellmunt J, Escudier B, Kim D, Stergiopoulos SG, Mietlowski W, Motzer RJ; RECORD-1 Trial Study Group. Survival prediction in everolimus-treated patients with metastatic renal cell carcinoma incorporating tumor burden response in the RECORD-1 trial. Eur Urol. 2013 Dec;64(6):994-1002. doi: 10.1016/j.eururo.2012.11.032. Epub 2012 Nov 21.
- Derived from this study: PubMed 22824201Stein A, Wang W, Carter AA, Chiparus O, Hollaender N, Kim H, Motzer RJ, Sarr C. Dynamic tumor modeling of the dose-response relationship for everolimus in metastatic renal cell carcinoma using data from the phase 3 RECORD-1 trial. BMC Cancer. 2012 Jul 23;12:311. doi: 10.1186/1471-2407-12-311.
- Derived from this study: PubMed 22342553Oudard S, Thiam R, Fournier LS, Medioni J, Lamuraglia M, Scotte F, Fabre E, Kim D, Kpamegan E, Panneerselvam A, Cuenod CA. Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study. Eur J Cancer. 2012 Jul;48(10):1512-8. doi: 10.1016/j.ejca.2012.01.027. Epub 2012 Feb 16.
- Derived from this study: PubMed 22297244Porta C, Calvo E, Climent MA, Vaishampayan U, Osanto S, Ravaud A, Bracarda S, Hutson TE, Escudier B, Grunwald V, Kim D, Panneerselvam A, Anak O, Motzer RJ. Efficacy and safety of everolimus in elderly patients with metastatic renal cell carcinoma: an exploratory analysis of the outcomes of elderly patients in the RECORD-1 Trial. Eur Urol. 2012 Apr;61(4):826-33. doi: 10.1016/j.eururo.2011.12.057. Epub 2012 Jan 5.
- Derived from this study: PubMed 22209391Calvo E, Escudier B, Motzer RJ, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Ravaud A, Kim D, Panneerselvam A, Anak O, Figlin RA. Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur J Cancer. 2012 Feb;48(3):333-9. doi: 10.1016/j.ejca.2011.11.027. Epub 2011 Dec 30.
- Derived from this study: PubMed 20194812White DA, Camus P, Endo M, Escudier B, Calvo E, Akaza H, Uemura H, Kpamegan E, Kay A, Robson M, Ravaud A, Motzer RJ. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010 Aug 1;182(3):396-403. doi: 10.1164/rccm.200911-1720OC. Epub 2010 Mar 1.
- Derived from this study: PubMed 18653228Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, Grunwald V, Thompson JA, Figlin RA, Hollaender N, Urbanowitz G, Berg WJ, Kay A, Lebwohl D, Ravaud A; RECORD-1 Study Group. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008 Aug 9;372(9637):449-56. doi: 10.1016/S0140-6736(08)61039-9. Epub 2008 Jul 22.
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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
93 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing RAD001 in people with Metastatic Renal Cell Carcinoma, run by Novartis Pharmaceuticals at 93 sites in 10 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 11 inclusion and 13 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 15 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 93 sites in United States, Japan, France, Italy, Canada and 5 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 15 Jan 2013). 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?
Progressive Free Survival (PFS) in Patients Who Receive RAD001 Plus Best Supportive Care(BSC) Versus Patients Who Receive Matching Placebo Plus BSC (time frame: Time from randomization to dates of disease progression, death from any cause or last tumor assessment reported between date of first patient randomized until 28Feb2008 cut of date.). 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 NCT00410124, which also lists 7 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 15 Jan 2013.