Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic CRC

Tracking Information
First Submitted Date ICMJE	April 11, 2006
First Posted Date ICMJE	April 12, 2006
Last Update Posted Date	February 2, 2012
Study Start Date ICMJE	September 2005
Primary Completion Date	Not Provided
Current Primary Outcome Measures ICMJE; (submitted: April 11, 2006)	overall response rate
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00313859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 11, 2006)	progression-free survival; overall survival; toxicity; duration of response
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic CRC
Official Title ICMJE	Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic Colorectal Cancer
Brief Summary	This trial is designed to assess the tolerability and efficacy of simvastatin plus FOLFIRI (irinotecan, 5-FU, leucovorin) in metastatic colorectal cancer patients.
Detailed Description	Progress in treatment for metastatic CRC has undoubtedly been achieved in the past decade. Until 1985, 5-fluorouracil (5-FU) was the only agent available for the treatment of metastatic CRC. Several trials have attempted to enhance the activity of bolus 5-FU, by the addition of levamisole or interferon. Despite of these attempts, no survival advantage was established until the introduction of the newer cytotoxic drugs. The addition of folinic acid (FA) to 5-FU, the use of infusional rather than bolus 5-FU, and the combination of new active agents such as irinotecan and oxaliplatin with 5-FU/FA have resulted in an increase in activity of 5-FU. In trials of current combination regimens as first-line therapy, response rates exceeding 30% and median survival duration longer than 16 months have been reported. In all, despite of rapid advances in the treatment of metastatic CRC during the last decade, the efficacy of treatment still needs to be improved. One potential way of increasing the survival of metastatic CRC patients is the introduction of a novel targeting agent to the standard cytotoxic regimen such as IFL (irinotecan, fluorouracil, and leucovorin). An increasingly recognized molecular target for anticancer treatment is the rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The end products of the mevalonate pathway are required for a number of essential cellular functions such as sterols for membrane integrity, ubiquinone for cell respiration, geranylgeranyl isoprenoids for covalent bindings to the ras family, dolichol for glycoprotein synthesis, and isopentenyladenine for tRNA function and protein synthesis. Fortunately, inhibitors of the key enzyme, the statins, are well established and have been used safely in the clinic for the treatment of hypercholesterolemia for decades. Therefore, HMG-CoA reductase may be a decent molecular target for anti-cancer therapy and statins may be readily applicable to the clinic once its potential role as an anticancer drug is established. The statins have recently gained attractions from medical oncologists because large retrospective analyses for efficacy trials of statins in coronary artery disease have shown that not only are these agents able to reduce cardiac disease-related mortality, but cancer incidence is also reduced by 28 - 33 %. In all, further clinical trials investigating on combining the standard treatment with these novel molecular targeting agents, the statins, are definitely warranted.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Colorectal Cancer; Metastasis
Intervention ICMJE	Drug: simvastatin
Study Arms	Not Provided
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 31, 2012)	50
Original Enrollment ICMJE; (submitted: April 11, 2006)	49
Actual Study Completion Date	August 2007
Primary Completion Date	Not Provided
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically or cytologically confirmed metastatic colorectal cancer; Age ≥ 18; ECOG performance status 0 - 2; At least one measurable lesion; Minimum life expectancy of 12 weeks; Adequate bone marrow reservoir (ANC ≥ 1500/㎕, platelet ≥ 100,000/㎕); Adequate renal function (serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 min/ml); Adequate liver functions (serum bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 3 times upper normal limits); No prior lipid-lowering therapy with statins less than 1 year before study entry; No prior chemo- or immunotherapy for metastatic CRC (adjuvant chemotherapy or chemoradiation therapy more than 6 months before study entry is permitted); Written informed consent Exclusion Criteria: Active infection requiring antibiotics therapy; Pregnancy and/or lactation; Other serious illness or medical condition not appropriate for chemotherapy, especially cardiovascular disease; Metastatic brain lesions; Receipt of radiotherapy within 2 weeks before the initiation of study treatment
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Korea, Republic of
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00313859
Other Study ID Numbers ICMJE	SMC IRB 2005-08-011
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Not Provided
Study Sponsor ICMJE	Samsung Medical Center
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Won Ki Kang, MD Samsung Medical Center
PRS Account	Samsung Medical Center
Verification Date	January 2012
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP