SCALOP-2: A multi-centre randomised study of induction chemotherapy followed by capecitabine (+/- nelfinavir) with high or standard dose radiotherapy for locally advanced non-metastatic pancreatic cancer

Abstract

Introduction: Chemotherapy followed by consolidation chemoradiotherapy (CRT) is a treatment option for locally advanced non‐metastatic pancreatic cancer (LAPC), but outcome remains poor. The SCALOP trial identified a feasible, safe, and effective CRT regimen for LAPC: capecitabine (830mg/m2 oral bd) as radiosensitisation + 50.4Gy in 28 fractions. The two‐stage SCALOP‐2 trial aims to improve this regimen by increasing radiotherapy dose intensity and adding nelfinavir as an additional radiosensitising AKT inhibitor. Methods: Patients with inoperable, histologically or cytologically proven LAPC are eligible for the study. All patients will receive three cycles of GEMABX (28‐day cycle of intravenous nab‐paclitaxel 125mg/m2 followed by intravenous gemcitabine 1000mg/m2 on days one, eight and fifteen). Those who have stable or responding disease assessed by RECIST V1.1 on CT scan, following three cycles of chemotherapy, will proceed to CRT. A safety run‐in stage with three dose levels, Stage 1, has been incorporated to establish the maximum tolerated dose (MTD) of nelfinavir to combine with the CRT regimen. Stage 1 opened for recruitment on 8th March 2016. Stage 2 will start once theMTD of nelfinavir is established. Approximately 262 patients will be recruited to ensure 170 patients (34 patients per arm) randomised to one of the five arms in a “2x2 factorial +1” Phase II design: capecitabine (830mg/m2 oral bd) + radiotherapy (50.4Gy in 28# or 60Gy in 30#)6nelfinavir, or chemotherapy only (two additional cycles of GEMABX). Patients randomised will first receive a fourth cycle of GEMABX. The primary objectives are to investigate if there is an improved 12‐month overall survival (OS) rate with increased radiotherapy dose intensity and improved progression‐free‐survival (PFS) with the addition of nelfinavir to CRT. Secondary endpoints include toxicity, quality of life, objective disease response, surgical resection rate (of primary tumour), treatment compliance, and CA19‐9. Radiotherapy trials quality assurance is enforced to ensure protocol compliance both at pre‐accrual and on‐trial stages. This comprises an on‐trial prospective centralised evaluation of contouring and planning. With an expected 65%of recruited patients being randomised, the sample size has a power of 90%and a one‐sided alpha of 5% to guarantee worthwhile effect of OS rate of 60%for both radiotherapy dose intensity, and to detect a rate of 80%for at least one radiotherapy dose intensity to take forward. Follow‐up will be at 26 weeks for participants in the chemotherapy only armand 30 weeks for participants in the other four randomised arms, and at 39 and 52 weeks from registration for all randomised patients, and 12‐weekly thereafter until last trial visit for the last participant. Results: Conclusion:.