Gefitinib With or Without Simvastatin in Non-Small Cell Lung Cancer (NSCLC)

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: NCT00452244
Recruitment Status : Completed
First Posted : March 27, 2007
Last Update Posted : August 25, 2017
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea

Brief Summary:
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 or disease Intervention/treatment Phase
Lung Cancer Drug: simvastatin Drug: gefitinib only Phase 2

Detailed Description:


  1. Sex (female vs. male)
  2. ECOG PS (0/1 vs. 2/3)
  3. Number of prior regimen (one vs. two).

Gefitinib (250 mg per day) + Simvastatin (40 mg per day) PO or Gefitinib (250 mg per day) alone

until progression or unacceptable toxicity

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : May 2006
Actual Primary Completion Date : February 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: study arm
Iressa (gefitinib) + simvastatin
Drug: simvastatin
Simvastatin 40mg/QD po daily every 3 weeks
Other Names:
  • simvarstar

Drug: gefitinib only
gefitinib 250mg/QD po daily every 3 weeks
Other Name: IRESSA

Active Comparator: control arm
Iressa (gefitinib) only
Drug: gefitinib only
gefitinib 250mg/QD po daily every 3 weeks
Other Name: IRESSA

Primary Outcome Measures :
  1. Overall Response rate [ Time Frame: every 8 weeks ]
    from C1D1 until confirmed disease progression

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: every 12 weeks ]
    the first day of treatment to death

  2. Toxicity [ Time Frame: every 4 weeks ]
    From C1D1 to 1 months after the last dose adminitration

  3. Pharmacogenetic and biomarker profile analysis [ Time Frame: every 8 weeks ]
    From screening visit until confirmed disease progression

  4. Time to progression [ Time Frame: every 8 weeks ]
    From randomization date to disease progresssion or death date

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologic or cytologic diagnosis of NSCLC
  2. Stage IV or selected stage IIIB (with positive pleural effusion or multiple ipsilateral lung nodules) according to the American Joint Committee on Cancer (AJCC).
  3. Previously treated with at least one platinum-based chemotherapy.
  4. Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
  5. Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
  6. No other forms of cancer therapy, such as radiation, immunotherapy for at least 2 weeks before the enrollment in study.
  7. Performance status of 0-3 on the ECOG criteria.
  8. At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 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:

  1. Presence of small-cell lung cancer alone or with NSCLC- Unresolved chronic toxic effects from previous anticancer therapy
  2. Known severe hypersensitivity to gefitinib or any of the tablet excipients
  3. Inability to swallow tablets
  4. Other coexisting malignant disease (apart from basal-cell carcinoma)
  5. More than three previous chemotherapy regimens for NSCLC
  6. Previous treatment with an experimental agent of which the main mechanism of action is inhibition of epidermal growth factor receptor or its associated tyrosine kinase
  7. Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John's wort; severe or uncontrolled systemic disease; clinically active interstitial lung disease (except uncomplicated lymphangitic carcinomatosis) pregnancy; and breastfeeding.
  8. MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
  9. Serious concomitant infection including post obstructive pneumonia
  10. Major surgery other than biopsy within the past two weeks.
  11. Pregnant or breast-feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00452244

Korea, Republic of
National Cancer Center, Korea
Goyang-si, Gyeonggi-do, Korea, Republic of
Sponsors and Collaborators
National Cancer Center, Korea
Principal Investigator: Ji-Youn Han, M.D.,Ph.D. National Cancer Center, Korea

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Ji-youn Han, Head, Center for Lung Cancer, National Cancer Center, Korea Identifier: NCT00452244     History of Changes
Other Study ID Numbers: NCCCTS-06-177
First Posted: March 27, 2007    Key Record Dates
Last Update Posted: August 25, 2017
Last Verified: August 2017

Keywords provided by Ji-youn Han, National Cancer Center, Korea:
Advanced NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors