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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastasis
• Intervention / Treatment: Drug: simvastatin

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: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
overall response rate

Secondary Outcome Measures

Outcome Measure
overall survival
toxicity
progression-free survival
duration of response

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: April 11, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (Estimate): April 12, 2006

Study Record Updates

• Last Update Posted (Estimate): February 2, 2012
• Last Update Submitted That Met QC Criteria: January 31, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: colorectal cancer; metastatic
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal 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: SMC IRB 2005-08-011