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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open Label, Stratified, Single-arm Phase II Study of Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumor (NET) After Failure of Cytotoxic Chemotherapy

Brief Summary: The purpose of this study was to assess the efficacy and safety of everolimus in the treatment of advanced pancreatic neuroendocrine tumor (NET) not responsive to cytotoxic chemotherapy. All patients were treated with everolimus until either tumor progression was documented using a standard criteria that measures tumor size called Response Evaluation Criteria in Solid tumors (RECIST), or until unacceptable toxicity occurred, or until the patient or investigator requested discontinuation of treatment.

Detailed Summary:

This was a stratified two-stage, single-arm, phase 2 study of treatment with everolimus in patients with advanced (unresectable or metastatic) pancreatic neuroendocrine tumor (NET) after failure of cytotoxic chemotherapy.

Stratum 1, consisted of patients not receiving chronic Octreotide Depot therapy, will receive everolimus monotherapy at 10 mg/day.

Stratum 2, consisting of patients with tumors that have progressed during Octreotide Depot treatment will continue their entry dose of Octreotide Depot plus everolimus 10 mg/day.


Sponsor: Novartis Pharmaceuticals

Current Primary Outcome: 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) ]

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.


Original Primary Outcome: Effect of everolimus on decreasing tumor size

Current Secondary Outcome:

  • 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 ]

    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

  • 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 ]

    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

  • 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) ]
    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.
  • 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 ]
    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
  • 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 ]
    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
  • 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 ]

    Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed.


    Original Secondary Outcome:

    • Duration of everolimus on tumor size
    • Effect of everolimus in combination with octreotide acetate on decreasing tumor size
    • The type, number and severity of side effects of everolimus alone,or everolimus in combination with octrotide acetate
    • Tracking the amount of everolimus in the blood over time and if it changes when given in combination with octreotide acetate for injection


    Information By: Novartis

    Dates:
    Date Received: August 2, 2006
    Date Started: June 2006
    Date Completion:
    Last Updated: May 6, 2013
    Last Verified: May 2013