None listed
Conditions
Brief summary
The primary purpose of this trial is to compare the effect of simvastatin with placebo on the effectiveness and side effects of pre-operative chemoradiotherapy treatment prior to rectal cancer surgery, and on the body's inflammatory response to cancer. Who is it for? You may be eligible to enroll in this trial if you are aged 18 or over and have been diagnosed with rectal adenocarcinoma or high grade dysplasia with radiological evidence of invasive tumour, for which pre-operative chemoradiotherapy treatment is planned. Study details All participants enrolled in this trial will be randomly allocated (by chance) to receive either the active simvastatin treatment in addition to their planned chemoradiotherapy treatment, or to receive an inactive placebo in addition to their planned chemoradiotherapy treatment. Participants will take the allocated treatment capsule once daily for 90 days starting one week before chemoradiotherapy. The study will last 3 years and participants will be asked to visit the clinic on nine occasions for clinical examinations and they will also have blood tests and magnetic resonance imaging (MRI) scans. Tumour tissue removed at the time of surgery will be assessed in the laboratory. It is hoped that if the study showed a positive outcome, then it may ultimately lead to patients in the future benefiting from adding simvastatin to chemoradiotherapy.
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 encapsula
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.
Sponsors
The Australasian Gastro-Intestinal Trials Group (AGITG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Exclusion criteria
1. Contraindications or hypersensitivity to statins, fluoropyrimidine chemotherapy or radiotherapy 2. Patients planned to receive oxaliplatin or biological agents (e.g. cetuximab) as part of pCRT 3. Taking statins in the 6 weeks before planned start of pCRT 4. Predicted life expectancy of less than 3 years 5. Prior pelvic or rectal radiotherapy 6. History of another malignancy within 5 years prior to registration. Patients with a past history of adequately treated carcinoma-in-situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or superficial transitional cell carcinoma of the bladder are eligible. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 5 years after definitive primary treatment 7. Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety 8. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol 9. 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 have been surgically sterilised or use a (double if required) barrier method of contraception.
Outcome results
None listed