This is a prospective, multicentre randomised, phase II clinical trial, with randomisation 2:1 by minimisation and stratification by tumour stage, planned chemotherapy and institution.

This is a prospective, multicentre randomised, phase II clinical trial to evaluate safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in patients with high-risk and borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). High risk defined as any patient with tumour >4cm, extrapancreatic extension or node positive disease.

Inclusion Criteria:

• Adults, aged between 18-75 years, with histological confirmation of pancreatic adenocarcinoma

• Any of the following

  1. T3 (tumour >4 cm)
  2. Extrapancreatic extension
  3. Node positive (stage IIB)
  4. Borderline resectable pancreatic cancer, locally advanced pancreatic cancer

• Measurable disease according to RECIST v1.1

• ECOG performance status 0-1

• Adequate renal and haematological function

• Adequate hepatic function. Defined as bilirubin <1.5 X ULN (Upper Limit of Normal), AST + ALT <3.0 X ULN. In patients who have had a recent biliary drainage and whose bilirubin is descending, a value of ≤ 3 X N is acceptable

• Study treatment planned to start within 14 days of registration

• Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments

• Signed, written informed consent

Exclusion Criteria:

• Tumour size greater than 70mm
• Prior abdominal radiotherapy
• Evidence of metastatic disease on baseline radiologic investigations
• History of another malignancy within 2 years prior to randomisation, except adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial transitional cell carcinoma of the bladder, or any Stage 1 endometrial carcinoma. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 2 years after definitive primary treatment
• Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
• Neuroendocrine pancreatic carcinoma
• Life expectancy of less than 3 months
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must use a reliable means of contraception
• Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol

The study will be conducted in accordance with applicable Privacy Acts and Regulations. All data generated in this study will remain confidential. All information will be stored securely at the NHMRC CTC, University of Sydney and will only be available to people directly involved with the study.

Personal data identifying trial participants will be held securely at the NHMRC CTC for the purpose of follow up if the patient is unable to/wishes to discontinue clinic based follow-up.