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Everolimus and Octreotide in Patients With Advanced Carcinoid Tumor (RADIANT-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: November 11, 2014
Last verified: November 2014
Results First Received: October 25, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Carcinoid Tumor
Malignant Carcinoid Syndrome
Interventions: Drug: Octreotide
Drug: Placebo
Drug: Everolimus

  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
Total 429 patients were randomized to double blind phase of treatment. 170 patients moved to the Open Label Phase.

Reporting Groups
  Description
Octreotide+ Everolimus Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Octreotide+ Placebo Followed by Open Label Arm Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1. Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.

Participant Flow for 2 periods

Period 1:   Double Blind Phase
    Octreotide+ Everolimus   Octreotide+ Placebo Followed by Open Label Arm
STARTED   216   213 
Safety Set   215 [1]   211 [2] 
COMPLETED   0   0 
NOT COMPLETED   216   213 
Disease Progression                101                154 
Adverse Event                61                16 
Final Primary Analysis                26                14 
Withdrawal by Subject                18                20 
Death                6                3 
Protocol Violation                3                4 
New Cander Therapy                1                1 
Lost to Follow-up                0                1 
[1] 1 patient did not provide at laest one valid post baseline safety assessment.
[2] 1 pt randomized never took drug Another randomized did not have valid post BL safety assessment

Period 2:   Open Label Phase
    Octreotide+ Everolimus   Octreotide+ Placebo Followed by Open Label Arm
STARTED   0   170 
COMPLETED   0   0 
NOT COMPLETED   0   170 
Disease Progression                0                86 
Adverse Event                0                46 
Withdrawal by Subject                0                15 
Administrative Problems                0                13 
Death                0                7 
Lost to Follow-up                0                2 
New Cancer Therapy                0                1 



  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
Octreotide+ Everolimus Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Octreotide+ Placebo Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.
Total Total of all reporting groups

Baseline Measures
   Octreotide+ Everolimus   Octreotide+ Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 216   213   429 
Age 
[Units: Years]
Mean (Standard Deviation)
 60.1  (10.72)   59.4  (11.13)   59.8  (10.92) 
Gender 
[Units: Participants]
     
Female   119   89   208 
Male   97   124   221 


  Outcome Measures
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1.  Primary:   Progression Free Survival (PFS) as Per Adjudicated Central Radiology Review   [ 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, 10 January 2007, until cut-off date 02 April 2010 ]

2.  Secondary:   Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)   [ 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, 10 January 2007, until cut-off date 02 April 2010 ]
  Hide Outcome Measure 2

Measure Type Secondary
Measure Title Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)
Measure Description The best overall response rate 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.
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, 10 January 2007, until cut-off date 02 April 2010  
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.
The Full Analysis Set (FAS; Intent-to-treat Population) consists of all randomized patients.

Reporting Groups
  Description
Octreotide+ Everolimus Everolimus was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity. Each treatment cycle lasted 28 days. Patients received their first dose of everolimus at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1, Day 1.
Octreotide+ Placebo Matching placebo was administered in accordance with a 10-mg daily dosing regimen (two 5-mg tablets) in conjunction with octreotide 30 mg intramuscularly (i.m.) every 28 days. Patients were treated until progression or unacceptable toxicity; Each treatment cycle lasted 28 days. Patients received their first dose of matching placebo at Cycle 1, Day 1. Administration of octreotide was performed every 28 days (± 4 days) starting on Cycle 1 Day 1.

Measured Values
   Octreotide+ Everolimus   Octreotide+ Placebo 
Participants Analyzed 
[Units: Participants]
 216   213 
Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST) 
[Units: Percentage of patients]
Number (95% Confidence Interval)
 2.3 
 (0.8 to 5.30) 
 1.9 
 (0.5 to 4.7) 

No statistical analysis provided for Best Overall Response Rate as Per Adjudicated Central Radiology Review Based on Response Evaluation Criteria in Solid Tumors (RECIST)



3.  Secondary:   Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline 5-hydroxyindoleacetic Acid (5-HIAA) Level   [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]

4.  Secondary:   Overall Survival Using Kaplan-Meier Methodology   [ Time Frame: Months 12, 24, 36, 48 ]

5.  Secondary:   Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Double-Blind Phase)   [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind ]

6.  Secondary:   Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs) (Open Label Phase)   [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind ]

7.  Secondary:   Progression Free Survival (PFS) as Per Adjudicated Central Review by Baseline Chromogranin A (CgA)   [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) reported between day of first patient randomised, 10 January 2007, until cut-off date 02 April 2010 ]


  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
No text entered.


  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


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

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00412061     History of Changes
Other Study ID Numbers: CRAD001C2325
2006-004507-18 ( EudraCT Number )
Study First Received: December 13, 2006
Results First Received: October 25, 2011
Last Updated: November 11, 2014
Health Authority: United States: Food and Drug Administration