AGITG MASTERPLAN: a randomised phase II study of modified FOLFIRINOX alone or in combination with stereotactic body radiotherapy for patients with high-risk and locally advanced pancreatic cancer

Abstract

Background: Among patients with non-metastatic pancreatic cancer, 80% have high-risk, borderline resectable or locally advanced cancer, with a 5-year overall survival of 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in these patients. Methods and design: MASTERPLAN is a multi-centre randomised phase II trial of 120 patients with histologically confirmed potentially operable pancreatic cancer (POPC) or inoperable pancreatic cancer (IPC). POPC includes patients with borderline resectable or high-risk tumours; IPC is defined as locally advanced or medically inoperable pancreatic cancer. Randomisation is 2:1 to chemotherapy + SBRT (investigational arm) or chemotherapy alone (control arm) by minimisation and stratified by patient cohort (POPC v IPC), planned induction chemotherapy and institution. Chemotherapy can have been commenced ≤28 days prior to randomisation. Both arms receive 6 × 2 weekly cycles of modified FOLFIRINOX (oxaliplatin (85 mg/m2 IV), irinotecan (150 mg/m2 ), 5-fluorouracil (2400 mg/m2 CIV), leucovorin (50 mg IV bolus)) plus SBRT in the investigational arm. Gemcitabine+nabpaclitaxel is permitted for patients unsuitable for mFOLFIRINOX. SBRT is 40Gy in five fractions with planning quality assurance to occur in real time. Following initial chemotherapy ± SBRT, resectability will be evaluated. For resected patients, adjuvant chemotherapy is six cycles of mFOLFIRINOX. Where gemcitabine+nabpaclitaxel was used initially, the adjuvant treatment is 12 weeks of gemcitabine and capecitabine or mFOLFIRINOX. Unresectable or medically inoperable patients with stable/responding disease will continue with a further six cycles of mFOLFIRINOX or three cycles of gemcitabine+nab-paclitaxel, whatever was used initially. The primary endpoint is 12-month locoregional control. Secondary endpoints are safety, surgical morbidity and mortality, radiological response rates, progression-free survival, pathological response rates, surgical resection rates, R0 resection rate, quality of life, deterioration-free survival and overall survival.