A clinical trial comparing Simvastatin to placebo, in addition to standard chemotherapy and radiotherapy, in preoperative treatment for patients with rectal cancer.
- Conditions
- Rectal CancerCancer - Bowel - Back passage (rectum) or large bowel (colon)
- Registration Number
- ACTRN12617001087347
- Lead Sponsor
- The Australasian Gastro-Intestinal Trials Group (AGITG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 222
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
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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<br>radiologist will be repeated on all remaining patients at the conclusion of the trial or prior to any publication of results.]
- Secondary Outcome Measures
Name Time Method