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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00412061
First received: December 13, 2006
Last updated: March 5, 2014
Last verified: March 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.

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.

Participant Flow:   Overall Study
    Octreotide+ Everolimus     Octreotide+ Placebo  
STARTED     216     213  
Safety Population     215     211  
COMPLETED     95 [1]   146  
NOT COMPLETED     121     67  
Ongoing, on study drug                 37                 34  
Adverse Event                 57                 14  
Withdrawn consent                 17                 11  
Death                 6                 2  
Protocol Violation                 3                 4  
New cancer therapy                 1                 1  
Lost to Follow-up                 0                 1  
[1] Patients listed as completed discontinued due to disease progression.



  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  
Number of Participants  
[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: patients]
     
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 ]
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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  
Number of 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:   Number of Patients With Adverse Events (AEs), Clinically Notable AE, Death, Serious Adverse Events (SAEs)   [ Time Frame: From first day of treatment up to 28 days after last day of treatment in double blind (safety data collected till data cut off date i.e. 2nd April 2010) ]

4.  Secondary:   Progression Free Survival (PFS) as Per Adjudicated Central Review by Change From Baseline Chromogranin A (CgA) and 5-hydroxyindoleacetic Acid (5-HIAA)   [ Time Frame: If elevated at baseline, evaluated every cycle visit (28 days/cycle) ]
Results not yet posted.   Anticipated Posting Date:   08/2013   Safety Issue:   No

5.  Secondary:   Overall Survival Using Kaplan-Meier Methodology   [ Time Frame: The date of randomization to the date of death ]
Results not yet posted.   Anticipated Posting Date:   08/2013   Safety Issue:   No

6.  Secondary:   Evaluation of Pharmacokinetics (PK)Parameters   [ Time Frame: Day 1 of every cycle (28 days/cycle) throughout the study ]
Results not yet posted.   Anticipated Posting Date:   08/2013   Safety Issue:   No


  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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