SPARC: A phase-I trial of pre-operative margin-intensified stereotactic radiotherapy for pancreatic cancer at high risk of positive resection margins.

Abstract

TPS536 Background: Standard therapy for resectable and borderline resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but clear resection margins rates are unsatisfactory. Conventional neoadjuvant radiotherapy has limited efficacy, but stereotactic radiotherapy (SBRT) achieves accuracy and precision to enable dose escalation and margin-intensification, with the goal of achieving clear resection margins. This prospective multi-centre study aims to establish the maximum tolerated dose of margin-intensified pre-operative SBRT, for subsequent definitive comparison with other neoadjuvant treatment options. Methods: SPARC is a phase-I dose-escalation study (NCT02308722). A ‘rolling-six’ design is utilised to minimise delays and facilitate ongoing recruitment during dose escalation. Eligibility comprises histologically or cytologically proven borderline-resectable pancreatic cancer, 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 is delivered in 5 daily fractions, with surgery planned to take place 5–6 weeks later. The margin-intense radiotherapy concept utilises a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration. Up to 4 radiotherapy dose levels will be investigated, and the maximum tolerated dose is the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. 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 and eleven patients have been treated to date. Cohort 1 was completed without DLT and recruitment to cohort 2 began in September 2016. Clinical trial information: NCT02308722.