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

NCT00452244 | Completed Phase 2

• 1 other identifier: NCCCTS-06-177
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

Keywords

Gefitinib; Simvastatin; NSCLC; Advanced NSCLC

Outcome Measures

Primary Outcomes (1)

• Overall Response rate

  from C1D1 until confirmed disease progression

  every 8 weeks

Secondary Outcomes (4)

• Overall survival

  every 12 weeks

• Toxicity

  every 4 weeks

• Pharmacogenetic and biomarker profile analysis

  every 8 weeks

• Time to progression

  every 8 weeks

Study Arms (2)

study arm

EXPERIMENTAL

Iressa (gefitinib) + simvastatin

Drug: simvastatin; Drug: gefitinib only

control arm

ACTIVE COMPARATOR

Iressa (gefitinib) only

Drug: gefitinib only

Interventions

simvastatin DRUG

Simvastatin 40mg/QD po daily every 3 weeks

Also known as: simvarstar, IRESSA

study arm

gefitinib only DRUG

gefitinib 250mg/QD po daily every 3 weeks

Also known as: IRESSA

control arm; study arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic or cytologic diagnosis of NSCLC
• Stage IV or selected stage IIIB (with positive pleural effusion or multiple ipsilateral lung nodules) according to the American Joint Committee on Cancer (AJCC).
• Previously treated with at least one platinum-based chemotherapy.
• Before study entry, a minimum of 21 days must have elapsed since any prior chemotherapy.
• Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease.
• No other forms of cancer therapy, such as radiation, immunotherapy for at least 2 weeks before the enrollment in study.
• Performance status of 0-3 on the ECOG criteria.
• At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 2000).- Estimated life expectancy of at least 8 weeks.
• Patient compliance that allow adequate follow-up.
• 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.
• Informed consent from patient or patient's relative.
• Males or females at least 18 years of age.
• 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.
• No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole.
• Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs

You may not qualify if:

• Presence of small-cell lung cancer alone or with NSCLC- Unresolved chronic toxic effects from previous anticancer therapy
• Known severe hypersensitivity to gefitinib or any of the tablet excipients
• Inability to swallow tablets
• Other coexisting malignant disease (apart from basal-cell carcinoma)
• More than three previous chemotherapy regimens for NSCLC
• 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
• 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.
• MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia
• Serious concomitant infection including post obstructive pneumonia
• Major surgery other than biopsy within the past two weeks.
• Pregnant or breast-feeding.

Sponsors & Collaborators

• National Cancer Center, Korea: lead

Study Sites (1)

National Cancer Center, Korea

Goyang-si, Gyeonggi-do, South Korea

Location

Related Publications (2)

• Han JY, Kim JY, Lee SH, Yoo NJ, Choi BG. Association between plasma hepatocyte growth factor and gefitinib resistance in patients with advanced non-small cell lung cancer. Lung Cancer. 2011 Nov;74(2):293-9. doi: 10.1016/j.lungcan.2011.02.021. Epub 2011 Mar 26.

  PMID: 21440951 DERIVED

• Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, Kim HT, Lee JS. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011 Mar 15;17(6):1553-60. doi: 10.1158/1078-0432.CCR-10-2525.

  PMID: 21411446 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Simvastatin; Gefitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ji-Youn Han, M.D.,Ph.D.

  National Cancer Center, Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, Center for Lung Cancer

Study Record Dates

• First Submitted: March 26, 2007
• First Posted: March 27, 2007
• Study Start: May 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2011
• Last Updated: August 25, 2017

Record last verified: 2017-08

Locations

KR (1)