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Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00363051
First received: August 2, 2006
Last updated: May 6, 2013
Last verified: May 2013
Results First Received: December 2, 2011  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Islet Cell Carcinoma
Neuroendocrine Carcinoma
Neuroendocrine Tumor
Pancreatic Neoplasms
Interventions: Drug: Everolimus 10 mg
Drug: Octreotide Depot

  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
No text entered.

Reporting Groups
  Description
Stratum 1: Everolimus 10 mg Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Stratum 2: Everolimus 10 mg + Octreotide Depot

Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.

Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.


Participant Flow:   Overall Study
    Stratum 1: Everolimus 10 mg     Stratum 2: Everolimus 10 mg + Octreotide Depot  
STARTED     115     45  
COMPLETED     77 [1]   23  
NOT COMPLETED     38     22  
Adminstrative problems                 1                 1  
Adverse Event                 21                 12  
New Cancer Therapy                 2                 1  
Withdrawal by Subject                 11                 3  
Lost to Follow-up                 0                 1  
Protocol Violation                 0                 2  
Death                 3                 2  
[1] Patients with documented disease progression per RECIST criteria



  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
Stratum 1: Everolimus 10 mg Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.
Total Total of all reporting groups

Baseline Measures
    Stratum 1: Everolimus 10 mg     Stratum 2: Everolimus 10 mg + Octreotide Depot     Total  
Number of Participants  
[units: participants]
  115     45     160  
Age  
[units: years]
Mean ± Standard Deviation
  55.1  ± 11.8     53.64  ± 12.478     54.33  ± 11.98  
Gender  
[units: participants]
     
Female     49     21     70  
Male     66     24     90  



  Outcome Measures
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1.  Primary:   Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months) ]

2.  Secondary:   Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review   [ Time Frame: from date of first documented confirmed response to time to progression, at least 3 months ]

3.  Secondary:   Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review   [ Time Frame: from date of first documented confirmed response to time to progression, at least 3 months ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review
Measure Description

Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR):

  • 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.

Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

Time Frame from date of first documented confirmed response to time to progression, at least 3 months  
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.
Very low number of patients demonstrated a partial response, the median duration of response as per central review has not been calculated.

Reporting Groups
  Description
Stratum 2: Everolimus 10 mg + Octreotide Depot

Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.

Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.


Measured Values
    Stratum 2: Everolimus 10 mg + Octreotide Depot  
Number of Participants Analyzed  
[units: participants]
  0  
Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review      

No statistical analysis provided for Duration of Overall Response (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review



4.  Secondary:   Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months) ]

5.  Secondary:   Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1]   [ Time Frame: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month ]

6.  Secondary:   Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2]   [ Time Frame: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month ]

7.  Secondary:   Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)   [ Time Frame: from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010 ]

8.  Secondary:   Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)   [ Time Frame: from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010 ]

9.  Secondary:   Time to Overall Survival (OS)(Stratum 1)   [ Time Frame: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012 ]

10.  Secondary:   Time to Overall Survival (OS) (Stratum 2)   [ Time Frame: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012 ]

11.  Secondary:   Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)   [ Time Frame: Cycle 1 Day 15 ]

12.  Secondary:   Effect of Octreotide Depot on the Trough Concentrations of Everolimus   [ Time Frame: Cycle 1 Day 1, Cycle 2 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