Abstract A001: Preoperative treatment with mFOLFIRINOX +/- isotoxic high-dose stereotactic body radiation therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): A randomized comparative multicenter phase II trial
Authors: Bouchart Christelle , Navez Julie , Borbath Ivan , Geboes Karen , Vandamme Timon , Closset Jean , Moretti Luigi , Demetter Pieter , Paesmans Marianne , Van Laethem Jean-Luc 
Published: January 2024

Abstract
Background: Surgical resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant therapy is a rapidly emerging concept that needs to be explored and validated in terms of therapeutic options and survival benefit. In this setting, preoperative modified FOLFIRINOX (mFFX) seems to be feasible and can be followed by radiation therapy with promising benefit for patients in terms of R0 resection, local control and survival. However, the best therapeutic sequence is not yet known and the role of adding high-dose SBRT to chemotherapy in the neoadjuvant strategy requires assessment in randomized trials. The aim of the study is to evaluate the impact and efficacy of adding isotoxic high-dose SBRT (iHD-SBRT) to neoadjuvant mFFX in patients with borderline resectable PDAC. Methods: This is a randomized comparative multicentre phase II trial, planning to enrol patients (n= 256) diagnosed with a borderline resectable biopsy-confirmed PDAC. Patients will receive 4 cycles of mFFX (or 6 doses of gemcitabine/nab-paclitaxel [Gem/Nab-P] in case of intolerance). After full disease restaging, non-progressive patients will be randomized for receiving either 4 additional mFFX cycles (or 6 doses of Gem/Nab-P) (Arm A), or 2 mFFX cycles (or 3 doses of Gem/Nab-P) + iHD-SBRT (35 to 55Gy in 5 fractions) + 2 mFFX cycles (or 3 doses of Gem/Nab-P) (Arm B). Then curative surgery will be performed followed by adjuvant chemotherapy according to patient’s condition. The co-primary endpoints are R0 resection and disease-free survival after the complete sequence strategy. The secondary endpoints include resection rate, overall survival, locoregional failure/distant metastasis free interval, pathologic complete response, toxicity, postoperative complications and quality of life assessment. Discussion: This trial will help define the best neoadjuvant treatment sequence for borderline resectable PDAC and aims to evaluate if a total neoadjuvant treatment integrating iHD-SBRT improves the patients’ oncological outcomes. Trial registration: The study was registered at ClinicalTrails.gov (NCT05083247) on October 19th, 2021, and in the Clinical Trials Information System (CTIS) EU CT database (2022-501181-22-01) on July 2022. The first patient was included on March 24, 2023.
Citation Format: Christelle Bouchart, Julie Navez, Ivan Borbath, Karen Geboes, Timon Vandamme, Jean Closset, Luigi Moretti, Pieter Demetter, Marianne Paesmans, Jean-Luc Van Laethem. Preoperative treatment with mFOLFIRINOX +/- isotoxic high-dose stereotactic body radiation therapy (iHD-SBRT) for borderline resectable pancreatic adenocarcinoma (the STEREOPAC trial): A randomized comparative multicenter phase II trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A001.