SPARC: A Phase I trial of pre-operative, margin intensive, stereotactic body radiation therapy (SBRT) for previously untreated borderline resectable pancreatic cancer
Odondi LET., Ward E., Holyoake D., Hamill C., Strauss V., Robinson M., Grose D., McIntosh D., Sebag-Montefiore D., Radhakrishna G., Mukherjee S., Hawkins M.
Background Standard therapy for borderline resectable pancreatic cancer (BRPC) in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins (R0) are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies has shown the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic body radiation therapy (SBRT) achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of R0 resection and local disease control. Methods SPARC is a “rolling-six” single-arm study designed to establish the maximum tolerated dose (MTD) for margin-intensive SBRT before resection of BRPC. Eligible patients will have histologically/cytologically proven previously untreated pancreatic cancer defined as borderline-resectable per NCCN criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. A maximum of 4 SBRT dose levels will be investigated to determine the MTD as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a Dose Limiting Toxicity (DLT). Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to SBRT in pancreatic cancer. Radiotherapy Quality Assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. Results Unavailable Conclusions Unavailable