Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (RADIANT-3)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00510068
First received: July 31, 2007
Last updated: June 4, 2015
Last verified: June 2015
Results First Received: November 11, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Advanced Neuroendocrine Tumors of Pancreatic Origin
Interventions: Drug: Everolimus
Drug: Everolimus 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
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Reporting Groups
  Description
Everolimus 10 mg/Day Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Placebo Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).

Participant Flow for 2 periods

Period 1:   Double-blind Period
    Everolimus 10 mg/Day     Placebo  
STARTED     207     203  
Safety Population     204     203  
COMPLETED     0     0  
NOT COMPLETED     207     203  
Disease progression                 98                 169  
Final primary analysis                 52                 18  
Adverse Event                 37                 7  
Withdrawal by Subject                 8                 6  
Death                 4                 3  
Abnormal test result (s)                 1                 0  
Lost to Follow-up                 1                 0  
Protocol Violation                 6                 0  

Period 2:   Open-label Period
    Everolimus 10 mg/Day     Placebo  
STARTED     225 [1]   0  
COMPLETED     0     0  
NOT COMPLETED     225     0  
Disease Progression                 124                 0  
Adverse Event                 46                 0  
Withdrawal by Subject                 21                 0  
Administrative problems                 17                 0  
Death                 7                 0  
New cancer therapy                 7                 0  
Protocol Violation                 2                 0  
Abnormal laboratory value (s)                 1                 0  
[1] 172 patients switched over from placebo & 53 who were initially randomized to Everolimus arm.



  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.
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Reporting Groups
  Description
Everolimus 10 mg/Day Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
Placebo Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
Total Total of all reporting groups

Baseline Measures
    Everolimus 10 mg/Day     Placebo     Total  
Number of Participants  
[units: participants]
  207     203     410  
Age  
[units: years]
Mean (Standard Deviation)
  57.1  (12.2)     56.2  (11.4)     56.6  (11.8)  
Age, Customized  
[units: Participants]
     
<65 years     146     153     299  
>=65 years     61     50     111  
Gender  
[units: participants]
     
Female     97     86     183  
Male     110     117     227  
Race/Ethnicity, Customized  
[units: Participants]
     
Caucasian     156     166     322  
Asian     40     34     74  
Black     9     2     11  
Other     2     1     3  



  Outcome Measures
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1.  Primary:   Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ]

2.  Secondary:   Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ]

3.  Secondary:   Overall Survival   [ Time Frame: Baseline, to death- no time limit ]

4.  Secondary:   Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ]

5.  Secondary:   Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ]

6.  Secondary:   Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response   [ Time Frame: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010 ]

7.  Secondary:   Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)   [ Time Frame: on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuation ]

8.  Secondary:   Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)   [ Time Frame: on or after the start of open-label study medication until no later than 28 days after open-label study medication discontinuation ]

9.  Secondary:   Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last   [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ]

10.  Secondary:   Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin   [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ]

11.  Secondary:   Evaluation of Pharmacokinetics (PK) Parameter: CL/F   [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ]

12.  Secondary:   Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration   [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ]

13.  Secondary:   Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier   [ Time Frame: 3 months, 6 months ]

14.  Secondary:   Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)   [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 ]

15.  Secondary:   Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)   [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 ]

16.  Secondary:   Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)   [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 ]

17.  Secondary:   Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)   [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 ]

18.  Secondary:   Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)   [ Time Frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 ]


  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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  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


No publications provided by Novartis

Publications automatically indexed to this study:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00510068     History of Changes
Other Study ID Numbers: CRAD001C2324, 2006-006819-75
Study First Received: July 31, 2007
Results First Received: November 11, 2011
Last Updated: June 4, 2015
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Associação Fundo de Incentivo à Pesquisa
Canada: Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ministry of Health and Welfare
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
South Korea: Korea Food and Drug Administration (KFDA)
Netherlands: Medical Ethics Review Committee (METC)
Slovakia: State Institute for Drug Control
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan: Center for Drug Evaluation
Thailand: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency