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 (RECORD-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00410124
First received: December 11, 2006
Last updated: December 7, 2012
Last verified: December 2012
Results First Received: October 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Metastatic Renal Cell Carcinoma
Interventions: Drug: RAD001
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Core period was terminated due to early achievements of efficacy targets and patients who were receiving study drug and patients receiving placebo in double blind phase had option to continue into the extension phase to receive open label RAD001.

Reporting Groups
  Description
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 at data cutoff of 28Feb2008, 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 + BSC / RAD001 Patients received matching placebo of RAD001 tablets twice a day along with Best Supportive Care. With the documented disease progression at data cutoff of 28Feb2008, 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.

Participant Flow for 2 periods

Period 1:   Core Phase Double Blind (15 Months)
    RAD001 +BSC     Placebo + BSC / RAD001  
STARTED     277 [1]   139  
Ongoing     13     4  
Completed Double Blind Treatment     62     2  
COMPLETED     75 [2]   6 [3]
NOT COMPLETED     202     133  
Adverse Event                 36                 2  
Abnormal Laboratory Value                 1                 0  
Protocol Violation                 2                 1  
Withdrawal by Subject                 13                 2  
Lost to Follow-up                 4                 0  
Administrative Problems                 2                 0  
Death                 7                 4  
Disease Progression                 137                 124  
[1] Started indicates randomized (FAS) and treated
[2] Patients ongoing/completed double blind phase had option entering extension phase continuing RAD001.
[3] All patients ongoing/completed/not completed in core had option to enter extension taking RAD001.

Period 2:   Extension Phase - Open Label (45 Months)
    RAD001 +BSC     Placebo + BSC / RAD001  
STARTED     67     111 [1]
COMPLETED     0     0  
NOT COMPLETED     67     111  
Adverse Event                 7                 19  
Abnormal Laboratory Values                 0                 1  
Abnormal Test Procedures                 0                 1  
Withdrawal by Subject                 1                 1  
Death                 2                 10  
Disease Progression                 56                 78  
Patient no longer required study drug                 1                 0  
Final Primary Analysis                 0                 1  
[1] Patients on placebo in core received RAD001 in extension phase.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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 + 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.
Total Total of all reporting groups

Baseline Measures
    RAD001 +BSC     Placebo + BSC     Total  
Number of Participants  
[units: participants]
  277     139     416  
Age, Customized  
[units: participants]
     
<65 years     165     98     263  
>=65 years     112     41     153  
Gender  
[units: participants]
     
Female     61     33     94  
Male     216     106     322  



  Outcome Measures
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1.  Primary:   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. ]

2.  Secondary:   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) ]

3.  Secondary:   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 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC
Measure Description 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.
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set was performed on the intent-to-treat population which consisted of all randomized patients.

Reporting Groups
  Description
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 at data cutoff of 28Feb2008, 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 + BSC Patients received matching placebo of RAD001 tablets twice a day along with Best Supportive Care. With the documented disease progression at data cutoff of 28Feb2008, 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.

Measured Values
    RAD001 +BSC     Placebo + BSC  
Number of Participants Analyzed  
[units: participants]
  277     139  
Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC  
[units: Percentage¬†of¬†Participants]
Number ( 95% Confidence Interval )
  1.8  
  ( 0.6 to 4.2 )  
  0.0  
  ( NA to NA ) [1]
[1] Upper and lower limit cannot be measured.

No statistical analysis provided for Best Overall Response Rate in Patients Who Receive RAD001 Plus BSC Versus Matching Placebo Plus BSC



4.  Secondary:   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 ]

5.  Secondary:   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 ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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. ]

9.  Secondary:   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. ]

10.  Secondary:   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. ]

11.  Secondary:   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. ]

12.  Secondary:   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. ]

13.  Secondary:   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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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