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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
History of Changes
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
No text entered.

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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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
  Show All Outcome Measures

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. ]
  Show Outcome Measure 1

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) ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments
Measure Description 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
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)  
Safety Issue Yes  

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  
Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments  
[units: Months]
Median ( 95% Confidence Interval ) 		  13.57  
  ( 11.96 to 17.87 )   		  13.01  
  ( 10.09 to 16.66 )  

No statistical analysis provided for Overall Survival (OS) Assessed by the Monthly Overall Survival Assessments



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 ]
  Show Outcome Measure 3

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 ]
  Show Outcome Measure 4

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 ]
  Show Outcome Measure 5

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 ]
  Show Outcome Measure 6

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 ]
  Show Outcome Measure 7

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. ]
  Show Outcome Measure 8

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. ]
  Show Outcome Measure 9

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. ]
  Show Outcome Measure 10

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. ]
  Show Outcome Measure 11

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. ]
  Show Outcome Measure 12

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. ]
  Show Outcome Measure 13


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Novartis Pharmaceuticals
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


No publications provided by Novartis

Publications automatically indexed to this study:


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00410124     History of Changes
Other Study ID Numbers: CRAD001C2240, 2006-002070-21
Study First Received: December 11, 2006
Results First Received: October 23, 2012
Last Updated: December 7, 2012
Health Authority: United States: Food and Drug Administration