A clinical trial comparing Simvastatin to placebo, in addition to standard chemotherapy and radiotherapy, in preoperative treatment for patients with rectal cancer.

Interventions: The statin chosen for this trial, simvastatin (SIM), is a well-known and widely available 3-hydroxy-3-methyl-glutaryl-coenzyme (HMG-CoA) reductase inhibitor commonly used in the treatment of hypercholesterolaemia and ischaemic heart disease. Simvastatin or placebo is the trial intervention.
Simvastatin will be given as a 40 mg capsule taken daily for 90 days, starting 1 week prior to first radiation dose for standard Preoperative chemoradiation (pCRT).
capsules, Simvastatin will be encapsulated in Swedish orange size DB AA” capsules, filled with microcrystalline cellulose powder. Patients will be asked to return unused drug and empty drug containers at the Week 13 visit (6 weeks post-pCRT). The number of capsules remaining will be counted by trial research staff and recorded to confirm adherence.
Primary outcome(s): To compare rates of favourable (grades 1-2) MRI-based tumour regression grading (by central review) following preoperative chemoradiation (pCRT)with Simvastatin or placebo, considering MRI-based tumour regression grading in 4 ordered categories: 1, 2, 3, 4-5.[Based on MRI 6–8 weeks after preoperative chemoradiation, an analysis of inter-observer agreement on mrTRG between site radiologists and a central
radiologist will be repeated on all remaining patients at the conclusion of the trial or prior to any publication of results.]
Study Design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Safety/efficacy