Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma (RECORD-3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00903175
First received: April 24, 2009
Last updated: May 20, 2016
Last verified: May 2016
Results First Received: May 20, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Renal Cell Carcinoma
Interventions: Drug: everolimus
Drug: sunitinib

  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
238 patients were randomized to everolimus as 1st line followed by 2nd line sunitinib. All patients in this group were treated. 233 patients were randomized to the sunitinib as 1st line followed by 2nd line everolimus. However 2 of the 233 patients were not treated in this group.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The trial had a crossover design: first-line therapy until disease progression followed by second-line therapy until disease progression.Patients were randomized 1:1 to either everolimus-sunitinib or sunitinib-everolimus treatment sequence and were stratified by MSKCC risk criteria

Reporting Groups
  Description
Everolimus 1L/Sunitinib 2L everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
Sunitinib 1L/Everolimus 2L sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment

Participant Flow for 2 periods

Period 1:   Period 1 - First Line
    Everolimus 1L/Sunitinib 2L     Sunitinib 1L/Everolimus 2L  
STARTED     238     231  
COMPLETED     161 [1]   142 [1]
NOT COMPLETED     77     89  
Adverse Event                 36                 50  
Abnormal lab value(s)                 0                 1  
Abnormal test procedure result(s)                 1                 0  
Protocol Violation                 3                 3  
Withdrawal by Subject                 8                 12  
Administrative problems                 12                 13  
Death                 17                 10  
[1] Completed = Disease progression (completed 1L)

Period 2:   Period 2 - Second Line
    Everolimus 1L/Sunitinib 2L     Sunitinib 1L/Everolimus 2L  
STARTED     128 [1]   116 [2]
COMPLETED     79 [3]   80 [3]
NOT COMPLETED     49     36  
Missing                 1                 0  
Adverse Event                 16                 20  
Withdrawal by Subject                 7                 5  
Lost to Follow-up                 1                 0  
Administrative problems                 19                 9  
Death                 5                 2  
[1] 139 from everolimus 1L planned to enter 2L period and cross over to sunitinib but only 128 did.
[2] 130 from Sunitinib 1L planned to enter 2L period and cross over to everolimus but only 116 did.
[3] Completed = Disease progression - (completed 2L)



  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.
The Full Analysis Set (FAS) consists of all randomized patients. Following the intent-to-treat principle, patients are analyzed according to the treatment sequence and stratum they were assigned to at randomization.

Reporting Groups
  Description
Everolimus 1L/Sunitinib 2L everolimus First Line: 10 mg orally, once daily, (two 5 mg tablets), continuous treatment. sunitinib Second Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2)
Sunitinib 1L/Everolimus 2L sunitinib First Line: 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off (4/2) everolimus Second Line: 10 mg orally, once daily (two 5 mg tablets), continuous treatment
Total Total of all reporting groups

Baseline Measures
    Everolimus 1L/Sunitinib 2L     Sunitinib 1L/Everolimus 2L     Total  
Number of Participants  
[units: participants]
  238     233     471  
Age  
[units: years]
Mean (Standard Deviation)
  61.36  (12.102)     60.84  (11.627)     61.10  (11.860)  
Gender, Customized  
[units: Participants]
     
Female     72     57     129  
Male     166     176     342  



  Outcome Measures
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1.  Primary:   Progression Free Survival First-Line (PFS 1-L)   [ Time Frame: Time from randomization to date of first disease progression or death during or after 1-L treatment, or last tumor assessment, reported between date of 1st participant randomized until 03-sep-2012, cutoff date (i.e. when 340 PFS-1L events were observed) ]

2.  Secondary:   Progression-free Survival Combined (PFS-C)   [ Time Frame: Time from randomization to date of 1st disease progression during or after 2-L treatment or date of death, or last tumor assessment, reported between date of 1st participant randomized until 3 years after last patient randomized (date cutoff : 16Jun2014) ]

3.  Secondary:   Overall Survival (OS)   [ Time Frame: Time from randomization to the date of death from any cause, reported between the date of first participant randomized and up to 3 years after the last participant randomized (date cutoff: 16Jun2014) ]

4.  Secondary:   Overall Response Rate (ORR) - First -Line (1-L)   [ Time Frame: time from first participant randomized until 03-sep-2012, cutoff date ]

5.  Secondary:   Duration of Response (DoR) - First-Line (1-L)   [ Time Frame: Time from first documented response date to date of disease progression, death from any cause during or after the 1-L period or last tumor assessment, reported between the date of first participant randomized until 03-sep-2012, cut-off date ]

6.  Secondary:   Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First-line Drug   [ Time Frame: Time from randomization to date of definitive deterioration (defined as no later increase above threshold observed during the 1-L period), or date of last assessment, reported between date of first patient randomized until 03-sep-2012, cutoff date) ]

7.  Secondary:   Time to Definitive Deterioration of the FKSI-DRS Risk Score by at Least 3 Score Units by First and Second-line Drugs Combined   [ Time Frame: Time from randomization to date of definitive deterioration (defined as no later increase above threshold observed during the 1-L or 2-L period), or date of last assessment, reported between date of first patient randomized until 03-sep-2012, cutoff date) ]

8.  Secondary:   Time to Definitive Deterioration of the Physical Functioning (PF) Scale of the EORTC QLQ-C30 - by First-Line (1L) Drug   [ Time Frame: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the 1-L period), or date of last assessment, reported between date of first patient randomized until 03-sep-2012, cutoff date ]

9.  Secondary:   Time to Definitive Deterioration of the Physical Functioning Scale of the EORTC QLQ-C30 - by First and Second-Line Drugs Combined   [ Time Frame: Time from randomization to date of definitive deterioration (defined as no later increase above threshold observed during the 1-L or 2-L period), or date of last assessment, reported between date of 1st patient randomized until 03-sep-2012, cutoff date ]

10.  Secondary:   Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First-Line Drug   [ Time Frame: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the 1-L period), or date of last assessment, reported between date of first patient randomized until 03-sep-2012, cutoff date ]

11.  Secondary:   Time to Definitive Deterioration of the Global Health Status/QoL Scores of the EORTC QLQ-C30 by First and Second-Line Drugs Combined   [ Time Frame: Time from randomization to date of definitive deterioration (defined as no later increase above threshold observed during the 1-L or 2-L period), or date of last assessment, reported between dates of 1st patient randomized until 03-sep-2012, cutoff date ]

12.  Secondary:   Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First-Line Drug   [ Time Frame: Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the 1-L period), or date of last assessment, reported between date of first patient randomized until 03-sep-2012, cutoff date ]

13.  Secondary:   Time to Definitive Deterioration of the Fatigue Scale of the EORTC QLQ-C30 by First and Second-Line Drugs Combined   [ Time Frame: Time from randomization to date of definitive deterioration (defined as no later increase above threshold observed during the 1-L or 2-L period), or date of last assessment, reported between date of 1st patient randomized until 03-sep-2012, cutoff date ]


  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
PRO Tools - completed on Days 1 & 28 of a cycle. Assessments on D1 coincided with end of a 14-day break for patients on sunitinib but not everolimus. So D1 assessments of patients in sunitinib arm may be less impacted by potential toxicity effects.


  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.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300
e-mail: trialandresults.registries@novartis.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00903175     History of Changes
Other Study ID Numbers: CRAD001L2202
2009-011056-21 ( EudraCT Number )
Study First Received: April 24, 2009
Results First Received: May 20, 2016
Last Updated: May 20, 2016
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Canada: Health Canada
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
France: Ministry of Health
Germany: Ministry of Health
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Spain: Ministry of Health