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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea
ClinicalTrials.gov Identifier:
NCT00452244
First received: March 26, 2007
Last updated: September 15, 2011
Last verified: September 2011

March 26, 2007
September 15, 2011
May 2006
February 2011   (final data collection date for primary outcome measure)
Overall Response rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
from C1D1 until confirmed disease progression
  • Time to progression
  • Tumor response rate
Complete list of historical versions of study NCT00452244 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]
    the first day of treatment to death
  • Toxicity [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
    From C1D1 to 1 months after the last dose adminitration
  • Pharmacogenetic and biomarker profile analysis [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    From screening visit until confirmed disease progression
  • Time to progression [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    From randomization date to disease progresssion or death date
  • Overall survival
  • Toxicity
  • Pharmacogenetic and biomarker study
Not Provided
Not Provided
 
Gefitinib With or Without Simvastatin in Non-Small Cell Lung Cancer (NSCLC)
Randomized Phase II Trail Comparing Gefitinib Plus Simvastatin and Gefitinib Alone in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC)

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.

Randomization

  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

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lung Cancer
  • Drug: simvastatin
    Simvastatin 40mg/QD po daily every 3 weeks
    Other Names:
    • simvarstar
    • IRESSA
  • Drug: gefitinib only
    gefitinib 250mg/QD po daily every 3 weeks
    Other Name: IRESSA
  • Experimental: study arm
    Iressa (gefitinib) + simvastatin
    Interventions:
    • Drug: simvastatin
    • Drug: gefitinib only
  • Active Comparator: control arm
    Iressa (gefitinib) only
    Intervention: Drug: gefitinib only

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
110
March 2011
February 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00452244
NCCCTS-06-177
No
Ji-youn Han, National Cancer Center, Korea
National Cancer Center, Korea
Not Provided
Principal Investigator: Ji-Youn Han, M.D.,Ph.D. National Cancer Center, Korea
National Cancer Center, Korea
September 2011

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