SPAR: This phase 2 trial is assessing the clinical benefit of adding a statin (Simvastatin) to standard chemotherapy and radiotherapy to treat patients with rectal cancer before surgeryA randomized, placebo-controlled phase II trial of Simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer

Inclusion

1. Males or females with biopsy proven rectal adenocarcinoma, or high-grade dysplasia with radiological evidence of invasive tumour
2. Distal border of the tumour is below the peritoneal reflection as assessed by MRI scan
3. Age more than or equal to 18 years
4. Clinical TNM tumour staging is T2-4 N0-2 M0 after staging investigations including CT scan of chest, abdomen and pelvis and pelvic MRI scan
5. Planned for concurrent long-course pCRT using fluoropyrimidine-based chemotherapy
6. Radiologically-measureable disease on baseline pelvic MRI scan
7. Adequate bone marrow function (e.g. platelets >100 x 109/L, neutrophils >1.5 x 109/L)
8. Adequate liver function (e.g. ALT/AST <3 x ULN, bilirubin <1.5 x ULN)
9. Adequate renal function (e.g. estimated creatinine clearance >50 ml/min)
10. Trial treatment planned to start within 28 days of randomisation
11. Diagnostic biopsy of rectal tumour is available for histological substudies
12. Willing and able to comply with all trial requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments (e.g. able to have IV contrast if this is required for tumour assessments)
13. Signed, written informed consent for the main trial