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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00313859
Recruitment Status : Completed
First Posted : April 12, 2006
Last Update Posted : February 2, 2012
Information provided by:
Samsung Medical Center

April 11, 2006
April 12, 2006
February 2, 2012
September 2005
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overall response rate
Same as current
Complete list of historical versions of study NCT00313859 on Archive Site
  • progression-free survival
  • overall survival
  • toxicity
  • duration of response
Same as current
Not Provided
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Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic CRC
Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic Colorectal Cancer
This trial is designed to assess the tolerability and efficacy of simvastatin plus FOLFIRI (irinotecan, 5-FU, leucovorin) in metastatic colorectal cancer patients.

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.

Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Colorectal Cancer
  • Metastasis
Drug: simvastatin
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
August 2007
Not Provided

Inclusion Criteria:

  1. Histologically or cytologically confirmed metastatic colorectal cancer
  2. Age ≥ 18
  3. ECOG performance status 0 - 2
  4. At least one measurable lesion
  5. Minimum life expectancy of 12 weeks
  6. Adequate bone marrow reservoir (ANC ≥ 1500/㎕, platelet ≥ 100,000/㎕)
  7. Adequate renal function (serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 50 min/ml)
  8. Adequate liver functions (serum bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 3 times upper normal limits)
  9. No prior lipid-lowering therapy with statins less than 1 year before study entry
  10. No prior chemo- or immunotherapy for metastatic CRC (adjuvant chemotherapy or chemoradiation therapy more than 6 months before study entry is permitted)
  11. Written informed consent

Exclusion Criteria:

  1. Active infection requiring antibiotics therapy
  2. Pregnancy and/or lactation
  3. Other serious illness or medical condition not appropriate for chemotherapy, especially cardiovascular disease
  4. Metastatic brain lesions
  5. Receipt of radiotherapy within 2 weeks before the initiation of study treatment
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
SMC IRB 2005-08-011
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Samsung Medical Center
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Principal Investigator: Won Ki Kang, MD Samsung Medical Center
Samsung Medical Center
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP