Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma

• Status: Not yet recruiting
• Trial end date: 2025-12-31

Summary

Background:Surgical resection is the only potentially curative treatment for patients with pancreatic cancer with the aim of curative R0 resection and related improvement of survival. As a standard, surgery is usually followed by adjuvant therapy that improves survival but neoadjuvant therapy (NAT) is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options, in both resectable and borderline resectable pancreatic tumors. In this setting, preoperative FFX seems to be feasible and can be prolonged by radiation therapy (chemoRT or SBRT) with promising benefits for patients in terms of R0 resection, local control and prolonged survival. However, the exact and best therapeutic sequence is not yet known and the additional role of adding radiation therapy to chemotherapy requires validation in randomised trials. We recently reported the feasibility and preliminary efficacy data of the whole therapeutic sequence combining preoperative FFX x 8 cycles (G-Nab-P in case of intolerance or no response ) prolonged by 5 days SBRT (35 Gy + SIB up to 50Gy at the tumour-vessel interfaces )[1, manuscript submitted]. We propose now to evaluate the impact and efficacy of adding isotoxic high-dose SBRT to preoperative neoadjuvant mFFX or Gem-NabP in patients with borderline or high-risk resectable pancreatic adenocarcinoma. We hypothesize that this full sequence strategy of pre-operative treatment is safe and feasible and will improve both the R0 resection rate and prognosis (DFS as primary end point) of pancreatic adenocarcinoma, especially by targeting the tumoural vascular encasement.

Objectives/endpoints: Evaluation of the safety and efficacy of pre-operative 8 cycles of modified FOLFIRINOX (or Gem-Nab-P) followed or not by SBRT in patients with borderline or at risk resectable pancreatic adenocarcinoma.

Primary objective:

• To compare DFS between arms

Secondary objectives:

To compare between the study arms:

• Resection rate

• R0 resection rate (> 1 mm)

• Overall survival (OS)

• Locoregional failure free interval (LFFI)

• Distant metastases free interval (DMFI)

• Complete feasibility of the therapeutic sequence

• Pathologic complete response rate (pCR)

• Toxicity (early and late)

• Postoperative complications rate

• Quality of life (QoL) assessment

• Phase: Phase 2

Details

• Lead Sponsor: Erasme University Hospital
• Collaborators: Academisch Ziekenhuis Groningen; Belgian Group of Digestive Oncology; Chirec; Pôle Hospitalier Jolimont; Universitair Ziekenhuis Brussel; University Hospital St Luc, Brussels; University Hospital, Ghent
• Treatments: Albumin-Bound Paclitaxel; Gemcitabine