Phase I study of proton therapy in adjuvant pancreatic cancer (PROTON-PANC).

Abstract

TPS4663 Background: Pancreatic adenocarcinoma (PAC) has a poor prognosis, with a 5-year survival rate of 10%. The current standard of care for patients with resectable disease is surgical resection followed by 6 months of adjuvant modified FOLFIRINOX (FFX, leucovorin, fluorouracil, irinotecan, and oxaliplatin). As survival outcomes and distant recurrence improve with the use of FFX, locoregional recurrence remains a cause of morbidity and mortality. We seek to integrate adjuvant short-course proton radiation therapy (PRT) to the surgical bed in between cycles of FFX. While there is limited literature on the combination of short course PRT and FFX, there are analogous experiences using 5 fraction SBRT or IMRT following FFX in routine clinical practice. The ongoing Alliance 021501 trial of preoperative chemotherapy vs. chemotherapy plus radiation (IMRT using 5 Gy X 5 or SBRT 6.6 X 5) in borderline resectable pancreatic cancer mandates that radiation starts 5 days or more following the last dose of FFX. Additionally, at the Lombardi Comprehensive Cancer Center, we routinely combine 5 fraction SBRT after a 10-14 day interval from FFX. Methods: This is a phase I, single-arm, open-label study. Eligible pts are ≥ 18 years old, have histologically confirmed, resected PAC of the pancreatic head (R0 or R1) on adjuvant FFX, an ECOG performance status of 0-1, and adequate normal bone marrow and hepato-renal function. Exclusion criteria are prior radiation to the upper abdomen (neoadjuvant chemotherapy is allowed). This study will use a 3+3 dose-escalation design to determine the safety and feasibility of combining 5 fractions of adjuvant PRT with FFX using different intervals between cycle 6 of FFX and PRT: dose level 1 uses a 12 day interval, and dose level 2 uses a 5 day interval. The primary endpoint is to determine the RP2D between the 2 proposed schedules. Using a 3+3 dose-escalation schema, 2-12 patients will be required to determine the RP2D. Enrollment began in Q4 2019. Clinical trial information: NCT03885284 .