Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

Phase 2

• Conditions: Adenocarcinoma of Rectum
• Interventions: Drug: simvastatin

• Registration Number: NCT02161822
• Lead Sponsor: Samsung Medical Center

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of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data).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

Study Timeline

• Study First Submitted: 2014-05-30
• Study First Submitted QC: 2014-06-10
• Study First Posted: 2014-06-12
• Study Start: 2014-10-01
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-23
• Last Update Posted: 2020-03-25
• Primary Completion: 2020-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simvastatin	simvastatin	single arm : Simvastatin

Primary Outcome Measures

Name	Time	Method
pathologic complete response rate	average of 5 weeks	pathologic complete response ratewill be shown with 95% confidence intervals

Secondary Outcome Measures

Name	Time	Method
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
lipid lowering effect of simvastatin	assessed up to 6 months	Total cholesterol, LDL-cholesterol records. (2weeks)
safety and toxicity	assessed up to 6 months	Response rate according to RECIST 1,1 guideline will also be evaluated
rate of sphincter-sparing surgical procedure	average of 5 weeks	rate of sphincter-sparing surgical procedure
rate of R0 resection	average of 5 weeks	rate of R0 resection (N-60)
pattern of failure	assessed up to 60 months	Sphincter preservation

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of