Adenocarcinoma of Rectum
Conditions
Keywords
locally advanced rectal cancer, neoadjuvant chemoradiation
Brief summary
Statins are widely used as lipid-lowering agents to lower cardiovascular risk with a favorable safety profile. In our recent in vitro study, the addition of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data). So we planned this study to investigate the synergistic effect of simvastatin combined with capecitabine and radiotherapy in locally advanced rectal cancer patients.
Detailed description
1. Primary Objective: pathologic complete response rate 2. Secondary Objectives: 1. rate of sphincter-sparing surgical procedure 2. rate of R0 resection 3. disease-free survival 4. overall survival 5. pattern of failure 6. safety and toxicity 7. lipid lowering effect of simvastatin
Interventions
DRUGsimvastatin
simvastatin 80mg qd for 5weeks
Sponsors
Samsung Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed adenocarcinoma of rectum * AJCC/UICC clinical stages of cT3-4 or cN+ * age ≥ 20 years * ECOG performance status 0-1 * No prior chemotherapy and radiotherapy * Adequate major organ functions as following: * Written informed consent * Willing and able to comply the protocol
Exclusion criteria
* Prior statins therapy within 1-year from the date of study entry * Uncontrolled or severe cardiovascular disease : New York Heart Association class III or IV heart disease Unstable angina or myocardial infarction within the past 6 months History of significant ventricular arrhythmia requiring medication with antiarrhythmics or significant conduction system abnormality. * Past or current history (within the last 5 years prior to treatment start) of other malignancies except rectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible) * Uncontrolled systemic illness such as DM, hypertension, hypothyroidism and infection * Pregnant nursing women (women of reproductive potential have to agree to use an effective contraceptive method) * Patients with CPK \> 5 X ULN at baseline * Concomitant use with clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, telithromycin, gemfibrozil, cyclosporine, danazol, amiodarone, verapamil
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pathologic complete response rate | average of 5 weeks | pathologic complete response ratewill be shown with 95% confidence intervals |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| rate of R0 resection | average of 5 weeks | rate of R0 resection (N-60) |
| disease-free survival | assessed up to 60 months | disease-free survival |
| overall survival | assessed up to 60 months | Time from randomization to death or last follow-up |
| rate of sphincter-sparing surgical procedure | average of 5 weeks | rate of sphincter-sparing surgical procedure |
| safety and toxicity | assessed up to 6 months | Response rate according to RECIST 1,1 guideline will also be evaluated |
| lipid lowering effect of simvastatin | assessed up to 6 months | Total cholesterol, LDL-cholesterol records. (2weeks) |
| pattern of failure | assessed up to 60 months | Sphincter preservation |
Countries
South Korea
Outcome results
None listed