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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00410124




Registration number
NCT00410124
Ethics application status
Date submitted
11/12/2006
Date registered
12/12/2006
Date last updated
15/01/2013

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2006-002070-21
Secondary ID [2] 0 0
CRAD001C2240
Universal Trial Number (UTN)
Trial acronym
RECORD-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - RAD001
Treatment: Drugs - Placebo

Experimental: RAD001 +BSC - 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.

Placebo Comparator: Placebo (plus BSC) - 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.


Treatment: Drugs: RAD001
The dose of RAD001 was 10 mg/day. Patients were instructed to take two tablets (5 mg each) by mouth every day.

Treatment: Drugs: Placebo


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
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 outcome [1] 0 0
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
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Baseline and every 28 days under treatment and at discontinuation from RAD001" until 28Feb2008 cutoff date
Secondary outcome [7] 0 0
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)
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
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-t
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
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.

Eligibility
Key inclusion criteria
- 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).

- 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
Minimum age
18 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Randwick
Recruitment hospital [3] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [4] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [5] 0 0
Novartis Investigative Site - Woodville
Recruitment hospital [6] 0 0
Novartis Investigative Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
5011 - Woodville
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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United States of America
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California
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Florida
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United States of America
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Indiana
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United States of America
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Kentucky
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United States of America
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Maryland
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United States of America
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Michigan
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Minnesota
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Missouri
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Nevada
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New York
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North Carolina
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United States of America
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Ohio
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United States of America
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Oregon
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Pennsylvania
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Texas
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Washington
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United States of America
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West Virginia
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Canada
State/province [19] 0 0
Alberta
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Canada
State/province [20] 0 0
Ontario
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Canada
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Quebec
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France
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Bordeaux Cedex
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France
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Lille Cedex
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France
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Lyon Cedex
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France
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Paris
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France
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Saint-Herblain Cédex
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France
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Strasbourg
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France
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Toulouse Cedex 3
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France
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Villejuif Cedex
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Germany
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Dresden
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Germany
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Frankfurt/M
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Germany
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Hannover
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Germany
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Kassel
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Germany
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Mainz
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Germany
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München
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Italy
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CR
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Italy
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GE
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Italy
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MI
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Italy
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MO
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Italy
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PG
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Italy
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PV
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Italy
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RM
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Italy
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Napoli
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Japan
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Ehime
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Japan
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Hokkaido
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Japan
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Ibaraki
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Shizuoka
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Japan
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Tochigi
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Japan
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Tokyo
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Japan
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Akita
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Japan
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Chiba
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Japan
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Fukuoka
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Japan
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Tokushima
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Netherlands
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Amsterdam
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Netherlands
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Leiden
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Netherlands
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Nijmegen
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Netherlands
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Utrecht
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Poland
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Gdañsk
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Poland
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Lodz
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Poland
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Warszawa
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Poland
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Wroclaw
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Spain
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Barcelona
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Spain
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Madrid
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Spain
State/province [66] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00410124
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications