NCT02246127

Sequentiality of Everolimus and STZ-5FU in Advanced Pancreatic Neuroendocrine Tumor

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 Progressive Pancreatic NETs (pNETs)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 141 (actual)
• Sponsor: Grupo Espanol de Tumores Neuroendocrinos · Academic / Other
• Sex: All
• Age: 18 Years – 94 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to compare streptozotocin (STZ) vs everolimus as first line treatment for advanced pNET and to elucidate which sequence of 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 description

STZ plus 5-Fuorouracil (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. This study was planned to compare STZ-5FU chemotherapy followed by everolimus upon progression versus the reverse sequence. However sequential studies with pNETs are hard to be managed in terms of time and costs. Therefore the protocol was amended to have PFS1 (progression free survival after course 1) as primary endpoint and PFS2 (i.e. progression free survival after both STZ based chemotherapy and Everolimus or the reverse order) as secondary endpoint. This information will be extremely valuable for the day to day clinical practice of pNETs oncologists

Conditions

• Neuroendocrine Tumors

Interventions

Type	Name	Description
DRUG	Drug: Everolimus	10mg/daily, oral. Number of Cycles: until progression or unacceptable toxicity develops.
DRUG	STZ-5FU	0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-5 every 6 weeks (Moertel) or 0,5g/m2 STZ on days 1-5 and 400mg/m2 5-FU on days 1-3, and then 1 day with 1g/m2 and 1 day 400mg/m2 5-FU every 3 weeks (Uppsala). Number of Cycles: until progression or unacceptable toxicity develops.

Timeline

• Start date: 2014-10-27
• Primary completion: 2020-11-18
• Completion: 2021-07-12
• First posted: 2014-09-22
• Last updated: 2025-05-11
• Results posted: 2025-05-11

Locations

37 sites across 8 countries: Denmark, France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom