Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

Study Overview
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Brief Summary
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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of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data).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
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Primary Objective: pathologic complete response rate Secondary Objectives: rate of sphincter-sparing surgical procedure rate of R0 resection disease-free survival overall survival pattern of failure safety and toxicity lipid lowering effect of simvastatin

Official Title
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A Single Arm, Phase II Study of Neoadjuvant Chemoradiotherapy With Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

Conditions
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Adenocarcinoma of Rectum

Intervention / Treatment
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* Drug: simvastatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin<br>single arm : Simvastatin | Drug: simvastatin<br>* simvastatin 80mg qd for 5weeks<br>* Other names: Zocor tab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic complete response rate | pathologic complete response ratewill be shown with 95% confidence intervals | average of 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of sphincter-sparing surgical procedure | rate of sphincter-sparing surgical procedure | average of 5 weeks | 
| rate of R0 resection | rate of R0 resection (N-60) | average of 5 weeks | 
| disease-free survival | disease-free survival | assessed up to 60 months | 
| overall survival | Time from randomization to death or last follow-up | assessed up to 60 months | 
| pattern of failure | Sphincter preservation | assessed up to 60 months | 
| safety and toxicity | Response rate according to RECIST 1,1 guideline will also be evaluated | assessed up to 6 months | 
| lipid lowering effect of simvastatin | Total cholesterol, LDL-cholesterol records. (2weeks) | assessed up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advanced rectal cancer, neoadjuvant chemoradiation