Ignite Creation Date:
2024-05-06 @ 7:00 PM
Last Modification Date:
2024-10-26 @ 2:58 PM
Study NCT ID:
NCT05861336
Status:
RECRUITING
Last Update Posted:
2024-01-05
First Post:
2023-03-21
Brief Title:
GEMNab-Paclitaxel Plus Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer
Sponsor:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Organization:
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
Study Overview
Official Title:
Phase II Study of Gemcitabine Plus Nab-Paclitaxel in Combination With Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer OVERPASS Trial
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OVERPASS
Brief Summary:
Single-arm prospective phase II study to evaluate safety and activity of an induction therapy with Gemcitabine GEM and nab-paclitaxel plus Losartan followed by Stereotactic Radiotherapy SBRT in patients affected by Locally Advanced Pancreatic Cancer LAPC
Detailed Description:
Pancreatic cancer PC is a malignant disease presenting high mortality rates with a 5-year survival of about 11 partly because of its known resistance to Chemotherapy CHT and Radiotherapy RT Radiation therapy in locally advanced and borderline resectable pancreatic cancer improves only local control as demonstrated by 5 studies published from 1980 to 2011 and confirmed by the more recent LAP-07 trial which investigated conventional RT after induction CHT with the same results
Losartan was administered because it indirectly affects tumor microenvironment mechanisms of chemo- and radioresistance PC cells through transforming growth factor-β TGF-β platelet-derived growth factor PDGF and Angiotensin II activating signaling pathways lead to tumor microenvironment TME cells activation like pancreatic stellate cells which play a key role in chemoresistance Angiotensin system and TGF-β increase and maintain the extracellular matrix which acts as a barrier against drugs Murphy et al showed that Losartan administration during chemotherapy resulted in an effective decrease in plasma levels of TGF-β Their unexpected successful results suggest that targeting not only tumor but also TME might be a novel treatment paradigm
The purpose of this study is to prospectively evaluate the safety and activity in terms of resectability rate of GEM-nab-paclitaxel chemotherapy with concurrent Losartan followed by SBRT in patients with LAPC
Secondary endpoints are margin-negative resection rate R0 progression-free survival PFS overall survival OS blood biomarkers response safety and quality of life A Carbohydrate antigen-199 CA199 reduction 15 from baseline to the end of induction therapy and Carcinoma embryonic antigen CEA are tested as a reliable prognostic factor
Losartan was administered because it indirectly affects tumor microenvironment mechanisms of chemo- and radioresistance PC cells through transforming growth factor-β TGF-β platelet-derived growth factor PDGF and Angiotensin II activating signaling pathways lead to tumor microenvironment TME cells activation like pancreatic stellate cells which play a key role in chemoresistance Angiotensin system and TGF-β increase and maintain the extracellular matrix which acts as a barrier against drugs Murphy et al showed that Losartan administration during chemotherapy resulted in an effective decrease in plasma levels of TGF-β Their unexpected successful results suggest that targeting not only tumor but also TME might be a novel treatment paradigm
The purpose of this study is to prospectively evaluate the safety and activity in terms of resectability rate of GEM-nab-paclitaxel chemotherapy with concurrent Losartan followed by SBRT in patients with LAPC
Secondary endpoints are margin-negative resection rate R0 progression-free survival PFS overall survival OS blood biomarkers response safety and quality of life A Carbohydrate antigen-199 CA199 reduction 15 from baseline to the end of induction therapy and Carcinoma embryonic antigen CEA are tested as a reliable prognostic factor
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None