Capecitabine Plus Simvastatin in Locally Advanced Rectal Cancer Patients

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

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of simvastatin to chemoradiotherapy with 5-FU showed synergistic anticancer effect in various colon cancer cells (unpublished data).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

Study Overview

• Status: Unknown
• Conditions: Adenocarcinoma of Rectum
• Intervention / Treatment: Drug: simvastatin

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-720
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin; single arm : Simvastatin	Drug: simvastatin; simvastatin 80mg qd for 5weeks; Other Names: Zocor tab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: woon ki kang, professor, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: May 30, 2014
• First Submitted That Met QC Criteria: June 10, 2014
• First Posted (Estimate): June 12, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2020
• Last Update Submitted That Met QC Criteria: March 23, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: locally advanced rectal cancer, neoadjuvant chemoradiation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 2014-03-056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes