Clinical Trial: Efficacy and Safety of Everolimus and (STZ-5FU) Given One Upfront the Other Upon Progression in Advanced pNET

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Randomized Open Label Study to Compare the Efficacy and Safety of Everolimus Followed by Chemotherapy With Streptozotocin- Fluorouracilo (STZ-5FU) Upon Progression or the Reverse Sequence, in Advanced

Brief Summary: The purpose of this study is to elucidate which sequence of streptozotocin (STZ) based chemotherapy and the mammalian Target of Rapamycin (mTOR) inhibitor, everolimus, gives better results in terms of second Progression Free Survival (PFS) in well differentiated and advanced pancreatic NETs.

Detailed Summary:

STZ based chemotherapy, STZ-5FU, is the actual standard of care for advanced pancreatic Neuroendocrine tumours (pNETS) in the European Union. Everolimus has been recently approved for its use in advanced pNETs by the Food and Drug Administration (FDA) and in Europe by the European Medical Agency (EMA).

A randomized study is needed to have a clear knowledge about the best sequence for its administration; this is, before or after palliative chemotherapy.

There may or may not be any benefits from giving first each other treatment of the study. The information obtained from this study will help the physician improve the treatment and management of patients with advanced pNET.


Sponsor: Grupo Espanol de Tumores Neuroendocrinos

Current Primary Outcome: Second Progression Free Survival (second PFS) [ Time Frame: Up to 140 +/- 8 weeks ]

PFS of Course 1 (PFS1) + interval between treatments + PFS of Course 2 (PFS2), where PFS1 represents progression free survival of Course 1 and PFS2 represents progression free survival of Course 2


Original Primary Outcome: Second Progression Free Survival (second PFS) [ Time Frame: Up to 84 weeks ]

PFS of Course 1 (PFS1) + interval between treatments + PFS of Course 2 (PFS2), where PFS1 represents progression free survival of Course 1 and PFS2 represents progression free survival of Course 2


Current Secondary Outcome:

  • Adverse events [ Time Frame: up to 30 days after 140 +/- 8 weeks ]
    Number of adverse events, dose reductions, and total dose administered of each treatment.
  • Time to first progression [ Time Frame: Up to 44 weeks to everolimus and up 96 weeks for STZ-5-FU. ]
    Time from the date of randomization to the date of first disease progression.
  • Ratio of incremental cost-efficacy (ICER) [ Time Frame: Up to 140+/-8 weeks ]
    Ratio of the difference of costs incurred on by each treatment arm and the difference of second progression free survival at each arm.
  • Response Rate (RR) [ Time Frame: Baseline and every 12 weeks up to 140+/-8 weeks ]
    Rate of objective response (= Complete response (CR)+ Partial Response (PR)+Stable Disease (SD)) measured by RECIST criteria version 1.0
  • Early Biochemical response [ Time Frame: Baseline and up to 4 weeks ]
    Levels of Chromogranin A (CgA)
  • Time to second progression [ Time Frame: Up to 140+/-8 weeks ]
    From the date of randomization to the date of second disease progression


Original Secondary Outcome:

  • Adverse events [ Time Frame: up to 30 days after 84 weeks ]
    Number of adverse events, dose reductions, and total dose administered of each treatment.
  • Time to first progression [ Time Frame: Up to 44 weeks to everolimus and up 40 weeks for STZ-5-FU. ]
    Time from the date of randomization to the date of first disease progression.
  • Ratio of incremental cost-efficacy (ICER) [ Time Frame: Up to 84 weeks. ]
    Ratio of the difference of costs incurred on by each treatment arm and the difference of second progression free survival at each arm.
  • Response Rate (RR) [ Time Frame: Baseline and every 12 weeks up to 84 weeks ]
    Rate of objective response (= Complete response (CR)+ Partial Response (PR)+Stable Disease (SD)) measured by RECIST criteria version 1.0
  • Early Biochemical response [ Time Frame: Baseline and up to 4 weeks ]
    Levels of Chromogranin A (CgA)
  • Time to second progression [ Time Frame: Up to 84 weeks. ]
    From the date of randomization to the date of second disease progression


Information By: Grupo Espanol de Tumores Neuroendocrinos

Dates:
Date Received: August 20, 2014
Date Started: October 2014
Date Completion: December 2018
Last Updated: November 3, 2015
Last Verified: November 2015