A Single Arm, Phase II Study of Neoadjuvant Chemoradiotherapy With Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients
Trial Snapshot
- Phase
- Phase 2
- Sponsor
- Samsung Medical Center
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- pathologic complete response rate
Study Overview
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of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data).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
-
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Simvastatin
single arm : Simvastatin
Intervention: simvastatin (Drug)
Outcomes
Primary Outcomes
pathologic complete response rate
Time Frame: average of 5 weeks
pathologic complete response ratewill be shown with 95% confidence intervals
Secondary Outcomes
- disease-free survival(assessed up to 60 months)
- overall survival(assessed up to 60 months)
- lipid lowering effect of simvastatin(assessed up to 6 months)
- safety and toxicity(assessed up to 6 months)
- rate of sphincter-sparing surgical procedure(average of 5 weeks)
- rate of R0 resection(average of 5 weeks)
- pattern of failure(assessed up to 60 months)
Investigators
Won Ki Kang
Samsung Medical Center
Samsung Medical Center