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: August 21, 2014
Last verified: August 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  
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: Participants]
     
Female     119     89     208  
Male     97     124     221  



  Outcome Measures
  Show All Outcome Measures

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 ]

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
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Time Frame No text entered.
Additional Description Double blind period, Safety Set consists all patients received at least one dose of study drug and who had at least one valid post-baseline safety assessment. The Open-label Set consists all patients received at least one dose of open-label everolimus and who had at least one valid safety assessment after initiation of open-label treatment

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Everolimus + Octreotide 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.
Placebo + Octreotide 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.
Everolimus Open Label Open Label - Patients who had progressive disease in this arm, can move to the open label Everolimus + depot octreotide by choice.

Other Adverse Events
    Everolimus + Octreotide     Placebo + Octreotide     Everolimus Open Label  
Total, other (not including serious) adverse events        
# participants affected / at risk     214/215     194/211     162/170  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     58/215 (26.98%)     21/211 (9.95%)     34/170 (20.00%)  
Leukopenia † 1      
# participants affected / at risk     16/215 (7.44%)     2/211 (0.95%)     2/170 (1.18%)  
Neutropenia † 1      
# participants affected / at risk     18/215 (8.37%)     3/211 (1.42%)     13/170 (7.65%)  
Thrombocytopenia † 1      
# participants affected / at risk     34/215 (15.81%)     1/211 (0.47%)     15/170 (8.82%)  
Gastrointestinal disorders        
Abdominal distension † 1      
# participants affected / at risk     12/215 (5.58%)     12/211 (5.69%)     10/170 (5.88%)  
Abdominal pain † 1      
# participants affected / at risk     65/215 (30.23%)     68/211 (32.23%)     43/170 (25.29%)  
Abdominal pain upper † 1      
# participants affected / at risk     22/215 (10.23%)     26/211 (12.32%)     16/170 (9.41%)  
Aphthous stomatitis † 1      
# participants affected / at risk     28/215 (13.02%)     3/211 (1.42%)     15/170 (8.82%)  
Ascites † 1      
# participants affected / at risk     17/215 (7.91%)     9/211 (4.27%)     8/170 (4.71%)  
Constipation † 1      
# participants affected / at risk     31/215 (14.42%)     22/211 (10.43%)     17/170 (10.00%)  
Diarrhoea † 1      
# participants affected / at risk     114/215 (53.02%)     77/211 (36.49%)     77/170 (45.29%)  
Dry mouth † 1      
# participants affected / at risk     22/215 (10.23%)     6/211 (2.84%)     7/170 (4.12%)  
Dysphagia † 1      
# participants affected / at risk     15/215 (6.98%)     5/211 (2.37%)     4/170 (2.35%)  
Flatulence † 1      
# participants affected / at risk     27/215 (12.56%)     28/211 (13.27%)     12/170 (7.06%)  
Haemorrhoids † 1      
# participants affected / at risk     17/215 (7.91%)     9/211 (4.27%)     9/170 (5.29%)  
Mouth ulceration † 1      
# participants affected / at risk     17/215 (7.91%)     5/211 (2.37%)     11/170 (6.47%)  
Nausea † 1      
# participants affected / at risk     92/215 (42.79%)     63/211 (29.86%)     60/170 (35.29%)  
Stomatitis † 1      
# participants affected / at risk     109/215 (50.70%)     25/211 (11.85%)     63/170 (37.06%)  
Vomiting † 1      
# participants affected / at risk     69/215 (32.09%)     40/211 (18.96%)     30/170 (17.65%)  
General disorders        
Asthenia † 1      
# participants affected / at risk     51/215 (23.72%)     30/211 (14.22%)     30/170 (17.65%)  
Chills † 1      
# participants affected / at risk     15/215 (6.98%)     10/211 (4.74%)     5/170 (2.94%)  
Fatigue † 1      
# participants affected / at risk     103/215 (47.91%)     91/211 (43.13%)     63/170 (37.06%)  
Oedema peripheral † 1      
# participants affected / at risk     92/215 (42.79%)     47/211 (22.27%)     62/170 (36.47%)  
Pyrexia † 1      
# participants affected / at risk     42/215 (19.53%)     21/211 (9.95%)     32/170 (18.82%)  
Infections and infestations        
Bronchitis † 1      
# participants affected / at risk     11/215 (5.12%)     7/211 (3.32%)     8/170 (4.71%)  
Nasopharyngitis † 1      
# participants affected / at risk     19/215 (8.84%)     26/211 (12.32%)     19/170 (11.18%)  
Sinusitis † 1      
# participants affected / at risk     12/215 (5.58%)     9/211 (4.27%)     17/170 (10.00%)  
Upper respiratory tract infection † 1      
# participants affected / at risk     27/215 (12.56%)     12/211 (5.69%)     11/170 (6.47%)  
Urinary tract infection † 1      
# participants affected / at risk     27/215 (12.56%)     16/211 (7.58%)     19/170 (11.18%)  
Investigations        
Alanine aminotransferase increased † 1      
# participants affected / at risk     9/215 (4.19%)     6/211 (2.84%)     10/170 (5.88%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     11/215 (5.12%)     8/211 (3.79%)     8/170 (4.71%)  
Blood creatinine increased † 1      
# participants affected / at risk     15/215 (6.98%)     5/211 (2.37%)     8/170 (4.71%)  
Weight decreased † 1      
# participants affected / at risk     59/215 (27.44%)     31/211 (14.69%)     33/170 (19.41%)  
Metabolism and nutrition disorders        
Decreased appetite † 1      
# participants affected / at risk     64/215 (29.77%)     36/211 (17.06%)     33/170 (19.41%)  
Dehydration † 1      
# participants affected / at risk     17/215 (7.91%)     12/211 (5.69%)     9/170 (5.29%)  
Hypercholesterolaemia † 1      
# participants affected / at risk     17/215 (7.91%)     6/211 (2.84%)     7/170 (4.12%)  
Hyperglycaemia † 1      
# participants affected / at risk     42/215 (19.53%)     9/211 (4.27%)     24/170 (14.12%)  
Hyperlipidaemia † 1      
# participants affected / at risk     15/215 (6.98%)     3/211 (1.42%)     4/170 (2.35%)  
Hypocalcaemia † 1      
# participants affected / at risk     17/215 (7.91%)     4/211 (1.90%)     11/170 (6.47%)  
Hypokalaemia † 1      
# participants affected / at risk     50/215 (23.26%)     8/211 (3.79%)     27/170 (15.88%)  
Hypomagnesaemia † 1      
# participants affected / at risk     15/215 (6.98%)     5/211 (2.37%)     6/170 (3.53%)  
Hypophosphataemia † 1      
# participants affected / at risk     11/215 (5.12%)     6/211 (2.84%)     8/170 (4.71%)  
Musculoskeletal and connective tissue disorders        
Arthralgia † 1      
# participants affected / at risk     38/215 (17.67%)     28/211 (13.27%)     19/170 (11.18%)  
Back pain † 1      
# participants affected / at risk     33/215 (15.35%)     41/211 (19.43%)     18/170 (10.59%)  
Muscle spasms † 1      
# participants affected / at risk     17/215 (7.91%)     13/211 (6.16%)     10/170 (5.88%)  
Musculoskeletal chest pain † 1      
# participants affected / at risk     18/215 (8.37%)     7/211 (3.32%)     11/170 (6.47%)  
Musculoskeletal pain † 1      
# participants affected / at risk     21/215 (9.77%)     21/211 (9.95%)     8/170 (4.71%)  
Myalgia † 1      
# participants affected / at risk     16/215 (7.44%)     14/211 (6.64%)     8/170 (4.71%)  
Pain in extremity † 1      
# participants affected / at risk     32/215 (14.88%)     24/211 (11.37%)     19/170 (11.18%)  
Nervous system disorders        
Dizziness † 1      
# participants affected / at risk     29/215 (13.49%)     24/211 (11.37%)     12/170 (7.06%)  
Dysgeusia † 1      
# participants affected / at risk     42/215 (19.53%)     12/211 (5.69%)     30/170 (17.65%)  
Headache † 1      
# participants affected / at risk     65/215 (30.23%)     49/211 (23.22%)     32/170 (18.82%)  
Psychiatric disorders        
Anxiety † 1      
# participants affected / at risk     14/215 (6.51%)     14/211 (6.64%)     12/170 (7.06%)  
Depression † 1      
# participants affected / at risk     16/215 (7.44%)     11/211 (5.21%)     12/170 (7.06%)  
Insomnia † 1      
# participants affected / at risk     20/215 (9.30%)     15/211 (7.11%)     12/170 (7.06%)  
Renal and urinary disorders        
Dysuria † 1      
# participants affected / at risk     12/215 (5.58%)     5/211 (2.37%)     7/170 (4.12%)  
Pollakiuria † 1      
# participants affected / at risk     10/215 (4.65%)     6/211 (2.84%)     11/170 (6.47%)  
Respiratory, thoracic and mediastinal disorders        
Cough † 1      
# participants affected / at risk     59/215 (27.44%)     32/211 (15.17%)     38/170 (22.35%)  
Dyspnoea † 1      
# participants affected / at risk     59/215 (27.44%)     19/211 (9.00%)     27/170 (15.88%)  
Dyspnoea exertional † 1      
# participants affected / at risk     9/215 (4.19%)     11/211 (5.21%)     7/170 (4.12%)  
Epistaxis † 1      
# participants affected / at risk     33/215 (15.35%)     5/211 (2.37%)     24/170 (14.12%)  
Oropharyngeal pain † 1      
# participants affected / at risk     20/215 (9.30%)     6/211 (2.84%)     13/170 (7.65%)  
Pleural effusion † 1      
# participants affected / at risk     12/215 (5.58%)     6/211 (2.84%)     7/170 (4.12%)  
Pneumonitis † 1      
# participants affected / at risk     20/215 (9.30%)     2/211 (0.95%)     6/170 (3.53%)  
Skin and subcutaneous tissue disorders        
Alopecia † 1      
# participants affected / at risk     13/215 (6.05%)     4/211 (1.90%)     7/170 (4.12%)  
Dry skin † 1      
# participants affected / at risk     23/215 (10.70%)     5/211 (2.37%)     9/170 (5.29%)  
Erythema † 1      
# participants affected / at risk     17/215 (7.91%)     4/211 (1.90%)     7/170 (4.12%)  
Hyperhidrosis † 1      
# participants affected / at risk     9/215 (4.19%)     13/211 (6.16%)     5/170 (2.94%)  
Onychoclasis † 1      
# participants affected / at risk     11/215 (5.12%)     1/211 (0.47%)     10/170 (5.88%)  
Pruritus † 1      
# participants affected / at risk     42/215 (19.53%)     12/211 (5.69%)     18/170 (10.59%)  
Rash † 1      
# participants affected / at risk     88/215 (40.93%)     37/211 (17.54%)     59/170 (34.71%)  
Vascular disorders        
Flushing † 1      
# participants affected / at risk     20/215 (9.30%)     20/211 (9.48%)     6/170 (3.53%)  
Hypertension † 1      
# participants affected / at risk     24/215 (11.16%)     21/211 (9.95%)     16/170 (9.41%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  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: NCT00412061     History of Changes
Other Study ID Numbers: CRAD001C2325, 2006-004507-18
Study First Received: December 13, 2006
Results First Received: October 25, 2011
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration