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

This study has been completed.
Sponsor:
Information provided by:
Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT00313859
First received: April 11, 2006
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

This trial is designed to assess the tolerability and efficacy of simvastatin plus FOLFIRI (irinotecan, 5-FU, leucovorin) in metastatic colorectal cancer patients.


Condition Intervention Phase
Colorectal Cancer
Metastasis
Drug: simvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Simvastatin Plus Irinotecan, Fluorouracil, and Leucovorin(FOLFIRI) for Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • overall response rate

Secondary Outcome Measures:
  • progression-free survival
  • overall survival
  • toxicity
  • duration of response

Enrollment: 50
Study Start Date: September 2005
Study Completion Date: August 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00313859

Locations
Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Samsung Medical Center
Investigators
Principal Investigator: Won Ki Kang, MD Samsung Medical Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00313859     History of Changes
Other Study ID Numbers: SMC IRB 2005-08-011
Study First Received: April 11, 2006
Last Updated: January 31, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Samsung Medical Center:
colorectal cancer
metastatic

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Fluorouracil
Simvastatin
Irinotecan
Leucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on August 19, 2014