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
  Purpose

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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Center, Korea:

Primary Outcome Measures:
  • Overall Response rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    from C1D1 until confirmed disease progression


Secondary Outcome Measures:
  • 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


Enrollment: 110
Study Start Date: May 2006
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: study arm
Iressa (gefitinib) + simvastatin
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
Active Comparator: control arm
Iressa (gefitinib) only
Drug: gefitinib only
gefitinib 250mg/QD po daily every 3 weeks
Other Name: IRESSA

Detailed Description:

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

  Eligibility

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

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.
  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: NCT00452244

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

No publications provided by National Cancer Center, Korea

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ji-youn Han, Head, Center for Lung Cancer, National Cancer Center, Korea
ClinicalTrials.gov Identifier: NCT00452244     History of Changes
Other Study ID Numbers: NCCCTS-06-177
Study First Received: March 26, 2007
Last Updated: September 15, 2011
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by National Cancer Center, Korea:
Gefitinib
Simvastatin
NSCLC
Advanced NSCLC

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

ClinicalTrials.gov processed this record on August 28, 2014