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
  Show All Outcome Measures

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 ]

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) ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title 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)
Measure Description Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from 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 randomization/start of treatment until first documented response confirmed 4 weeks later (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.
Full Analysis Set (FAS) was consisted of all patients who received at least one dose of everolimus.

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]
  45  
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)  
[units: percentage¬†of¬†participants]
Number ( 95% Confidence Interval )
  4.4  
  ( 0.5 to 15.1 )  

No statistical analysis provided for 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)



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


  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.


Limitations and Caveats
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.  


Results Point of Contact:  
Name/Title: Novartis Study Director
Organization: Novartis Pharmaceuticals
phone: (862 778-8300


No publications provided


Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00363051     History of Changes
Other Study ID Numbers: CRAD001C2239
Study First Received: August 2, 2006
Results First Received: December 2, 2011
Last Updated: May 6, 2013
Health Authority: United States: Food and Drug Administration