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 ]

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
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Time Frame No text entered.
Additional Description The Safety Set consists of all patients who received at least one dose of study drug and who had at least one valid post-baseline safety assessment. The “other adverse events” table includes only non-serious adverse events.

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

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.

Other Adverse Events
    Octreotide+ Everolimus     Octreotide + Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     214/215     194/211  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     58/215 (26.98%)     21/211 (9.95%)  
Leukopenia † 1    
# participants affected / at risk     16/215 (7.44%)     2/211 (0.95%)  
Neutropenia † 1    
# participants affected / at risk     18/215 (8.37%)     3/211 (1.42%)  
Thrombocytopenia † 1    
# participants affected / at risk     32/215 (14.88%)     1/211 (0.47%)  
Gastrointestinal disorders      
Abdominal distension † 1    
# participants affected / at risk     12/215 (5.58%)     12/211 (5.69%)  
Abdominal pain † 1    
# participants affected / at risk     63/215 (29.30%)     68/211 (32.23%)  
Abdominal pain upper † 1    
# participants affected / at risk     22/215 (10.23%)     26/211 (12.32%)  
Aphthous stomatitis † 1    
# participants affected / at risk     27/215 (12.56%)     3/211 (1.42%)  
Ascites † 1    
# participants affected / at risk     16/215 (7.44%)     9/211 (4.27%)  
Constipation † 1    
# participants affected / at risk     31/215 (14.42%)     22/211 (10.43%)  
Diarrhoea † 1    
# participants affected / at risk     114/215 (53.02%)     75/211 (35.55%)  
Dry mouth † 1    
# participants affected / at risk     21/215 (9.77%)     6/211 (2.84%)  
Dysphagia † 1    
# participants affected / at risk     15/215 (6.98%)     5/211 (2.37%)  
Flatulence † 1    
# participants affected / at risk     27/215 (12.56%)     28/211 (13.27%)  
Haemorrhoids † 1    
# participants affected / at risk     17/215 (7.91%)     9/211 (4.27%)  
Mouth ulceration † 1    
# participants affected / at risk     17/215 (7.91%)     6/211 (2.84%)  
Nausea † 1    
# participants affected / at risk     89/215 (41.40%)     63/211 (29.86%)  
Stomatitis † 1    
# participants affected / at risk     109/215 (50.70%)     24/211 (11.37%)  
Vomiting † 1    
# participants affected / at risk     69/215 (32.09%)     39/211 (18.48%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     51/215 (23.72%)     30/211 (14.22%)  
Chills † 1    
# participants affected / at risk     15/215 (6.98%)     8/211 (3.79%)  
Fatigue † 1    
# participants affected / at risk     102/215 (47.44%)     91/211 (43.13%)  
Oedema peripheral † 1    
# participants affected / at risk     90/215 (41.86%)     45/211 (21.33%)  
Pyrexia † 1    
# participants affected / at risk     41/215 (19.07%)     21/211 (9.95%)  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     11/215 (5.12%)     6/211 (2.84%)  
Nasopharyngitis † 1    
# participants affected / at risk     19/215 (8.84%)     26/211 (12.32%)  
Sinusitis † 1    
# participants affected / at risk     11/215 (5.12%)     9/211 (4.27%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     27/215 (12.56%)     10/211 (4.74%)  
Urinary tract infection † 1    
# participants affected / at risk     26/215 (12.09%)     16/211 (7.58%)  
Investigations      
Aspartate aminotransferase increased † 1    
# participants affected / at risk     11/215 (5.12%)     8/211 (3.79%)  
Blood creatinine increased † 1    
# participants affected / at risk     14/215 (6.51%)     5/211 (2.37%)  
Weight decreased † 1    
# participants affected / at risk     59/215 (27.44%)     28/211 (13.27%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     64/215 (29.77%)     36/211 (17.06%)  
Dehydration † 1    
# participants affected / at risk     16/215 (7.44%)     12/211 (5.69%)  
Hypercholesterolaemia † 1    
# participants affected / at risk     15/215 (6.98%)     6/211 (2.84%)  
Hyperglycaemia † 1    
# participants affected / at risk     40/215 (18.60%)     9/211 (4.27%)  
Hyperlipidaemia † 1    
# participants affected / at risk     14/215 (6.51%)     2/211 (0.95%)  
Hypocalcaemia † 1    
# participants affected / at risk     17/215 (7.91%)     3/211 (1.42%)  
Hypokalaemia † 1    
# participants affected / at risk     50/215 (23.26%)     7/211 (3.32%)  
Hypomagnesaemia † 1    
# participants affected / at risk     15/215 (6.98%)     4/211 (1.90%)  
Hypophosphataemia † 1    
# participants affected / at risk     11/215 (5.12%)     5/211 (2.37%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     38/215 (17.67%)     28/211 (13.27%)  
Back pain † 1    
# participants affected / at risk     33/215 (15.35%)     39/211 (18.48%)  
Muscle spasms † 1    
# participants affected / at risk     16/215 (7.44%)     13/211 (6.16%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     18/215 (8.37%)     7/211 (3.32%)  
Musculoskeletal pain † 1    
# participants affected / at risk     20/215 (9.30%)     22/211 (10.43%)  
Myalgia † 1    
# participants affected / at risk     16/215 (7.44%)     14/211 (6.64%)  
Pain in extremity † 1    
# participants affected / at risk     32/215 (14.88%)     25/211 (11.85%)  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     29/215 (13.49%)     23/211 (10.90%)  
Dysgeusia † 1    
# participants affected / at risk     42/215 (19.53%)     12/211 (5.69%)  
Headache † 1    
# participants affected / at risk     65/215 (30.23%)     48/211 (22.75%)  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     14/215 (6.51%)     13/211 (6.16%)  
Depression † 1    
# participants affected / at risk     16/215 (7.44%)     10/211 (4.74%)  
Insomnia † 1    
# participants affected / at risk     20/215 (9.30%)     13/211 (6.16%)  
Renal and urinary disorders      
Dysuria † 1    
# participants affected / at risk     12/215 (5.58%)     4/211 (1.90%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     59/215 (27.44%)     31/211 (14.69%)  
Dyspnoea † 1    
# participants affected / at risk     59/215 (27.44%)     18/211 (8.53%)  
Dyspnoea exertional † 1    
# participants affected / at risk     9/215 (4.19%)     11/211 (5.21%)  
Epistaxis † 1    
# participants affected / at risk     33/215 (15.35%)     4/211 (1.90%)  
Oropharyngeal pain † 1    
# participants affected / at risk     20/215 (9.30%)     6/211 (2.84%)  
Pleural effusion † 1    
# participants affected / at risk     12/215 (5.58%)     5/211 (2.37%)  
Pneumonitis † 1    
# participants affected / at risk     18/215 (8.37%)     2/211 (0.95%)  
Skin and subcutaneous tissue disorders      
Alopecia † 1    
# participants affected / at risk     13/215 (6.05%)     4/211 (1.90%)  
Dry skin † 1    
# participants affected / at risk     23/215 (10.70%)     5/211 (2.37%)  
Erythema † 1    
# participants affected / at risk     17/215 (7.91%)     4/211 (1.90%)  
Hyperhidrosis † 1    
# participants affected / at risk     9/215 (4.19%)     13/211 (6.16%)  
Onychoclasis † 1    
# participants affected / at risk     11/215 (5.12%)     1/211 (0.47%)  
Pruritus † 1    
# participants affected / at risk     41/215 (19.07%)     12/211 (5.69%)  
Rash † 1    
# participants affected / at risk     88/215 (40.93%)     37/211 (17.54%)  
Vascular disorders      
Flushing † 1    
# participants affected / at risk     20/215 (9.30%)     19/211 (9.00%)  
Hypertension † 1    
# participants affected / at risk     24/215 (11.16%)     20/211 (9.48%)  
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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