Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
National Cancer Center, Korea |
---|---|
Information provided by: | National Cancer Center, Korea |
ClinicalTrials.gov Identifier: | NCT00452244 |
The epidermal growth factor receptor (EGFR) is a key regulator of growth, differentiation, and survival of epithelial cancers. In a small subset of tumors, the presence of activating mutations within the ATP binding site confers increased susceptibility to gefitinib, a potent tyrosine kinase inhibitor of EGFR. Agents that can inhibit EGFR function through different mechanisms may enhance gefitinib activity in patients lacking these mutations. Mevalonate metabolites play significant roles in the function of the EGFR; therefore, mevalonate pathway inhibitors may potentiate EGFR-targeted therapies. Targeting HMG-CoA reductase, the rate-limiting enzyme of mevalonate pathway, using lovastatin induces a potent apoptosis in a variety of tumor types. In an in vitro study, combining gefitinib and lovastatin treatment showed synergistic cytotoxic activity through enhanced inhibition of AKT activation by EGF in NSCLC and head & neck cancer cell lines. Therefore, the investigators would like to compare the combination effect of gefitinib and simvastatin, the specific and protein inhibitor of HMG-CoA reductase, with gefitinib alone in previously treated patients with NSCLC.
Condition | Intervention | Phase |
---|---|---|
Lung Cancer |
Drug: simvastatin Drug: gefitinib only |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study |
Official Title: | Randomized Phase II Trail Comparing Gefitinib Plus Simvastatin and Gefitinib Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC) |
Estimated Enrollment: | 94 |
Study Start Date: | May 2006 |
Estimated Study Completion Date: | February 2009 |
Estimated Primary Completion Date: | February 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1: Experimental
Iressa (gefitinib) + simvastatin
|
Drug: simvastatin
Simvastatin 40mg/QD po daily every 3 weeks
Drug: gefitinib only
gefitinib 250mg/QD po daily every 3 weeks
|
2: Active Comparator
Iressa (gefitinib) only
|
Drug: gefitinib only
gefitinib 250mg/QD po daily every 3 weeks
|
Randomization
Gefitinib (250 mg per day) + Simvastatin (40 mg per day) PO or Gefitinib (250 mg per day) alone
until progression or unacceptable toxicity
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
2000).- Estimated life expectancy of at least 8 weeks. 9)Patient compliance that allow adequate follow-up. 10)Adequate hematologic (ANC count ≥ 1,000/uL, platelet count ≥ 150,000/mm3), hepatic (bilirubin level≤1.5 mg/dL, AST/ALT ≤ 80 IU/L), and renal (creatinine concentration ≤ 1.5 mg/dL) function.
11)Informed consent from patient or patient's relative. 12)Males or females at least 18 years of age. 13)If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment. 14)No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole. 15)Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs
Exclusion Criteria:
Korea, Republic of, Gyeonggi-do | |
National Cancer Center, Korea | |
Goyang-si, Gyeonggi-do, Korea, Republic of |
Principal Investigator: | Ji-Youn Han, M.D.,Ph.D. | National Cancer Center, Korea |
Responsible Party: | National Cancer Center, Korea ( Ji-Youn Han ) |
Study ID Numbers: | NCCCTS-06-177 |
Study First Received: | March 26, 2007 |
Last Updated: | January 13, 2009 |
ClinicalTrials.gov Identifier: | NCT00452244 History of Changes |
Health Authority: | South Korea: Korea Food and Drug Administration (KFDA) |
Gefitinib Simvastatin NSCLC Advanced NSCLC |
Thoracic Neoplasms Antimetabolites Simvastatin Antilipemic Agents Anticholesteremic Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Protein Kinase Inhibitors Carcinoma |
Respiratory Tract Diseases Lung Neoplasms Lung Diseases Non-small Cell Lung Cancer Carcinoma, Non-Small-Cell Lung Gefitinib Neoplasms, Glandular and Epithelial |
Antimetabolites Thoracic Neoplasms Respiratory Tract Neoplasms Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Simvastatin Antilipemic Agents Enzyme Inhibitors Anticholesteremic Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Protein Kinase Inhibitors |
Pharmacologic Actions Carcinoma Neoplasms Neoplasms by Site Respiratory Tract Diseases Lung Neoplasms Therapeutic Uses Lung Diseases Carcinoma, Non-Small-Cell Lung Gefitinib Neoplasms, Glandular and Epithelial |