- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00452244
Gefitinib With or Without Simvastatin in Non-Small Cell Lung Cancer (NSCLC)
24. august 2017 opdateret af: Ji-youn Han, National Cancer Center, Korea
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.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Randomization
- Sex (female vs. male)
- ECOG PS (0/1 vs. 2/3)
- 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
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
110
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Gyeonggi-do
-
Goyang-si, Gyeonggi-do, Korea, Republikken
- National Cancer Center, Korea
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: study arm
Iressa (gefitinib) + simvastatin
|
Simvastatin 40mg/QD po daily every 3 weeks
Andre navne:
gefitinib 250mg/QD po daily every 3 weeks
Andre navne:
|
Aktiv komparator: control arm
Iressa (gefitinib) only
|
gefitinib 250mg/QD po daily every 3 weeks
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Overall Response rate
Tidsramme: every 8 weeks
|
from C1D1 until confirmed disease progression
|
every 8 weeks
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Overall survival
Tidsramme: every 12 weeks
|
the first day of treatment to death
|
every 12 weeks
|
Toxicity
Tidsramme: every 4 weeks
|
From C1D1 to 1 months after the last dose adminitration
|
every 4 weeks
|
Pharmacogenetic and biomarker profile analysis
Tidsramme: every 8 weeks
|
From screening visit until confirmed disease progression
|
every 8 weeks
|
Time to progression
Tidsramme: every 8 weeks
|
From randomization date to disease progresssion or death date
|
every 8 weeks
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Ji-Youn Han, M.D.,Ph.D., National Cancer Center, Korea
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. maj 2006
Primær færdiggørelse (Faktiske)
1. februar 2011
Studieafslutning (Faktiske)
1. marts 2011
Datoer for studieregistrering
Først indsendt
26. marts 2007
Først indsendt, der opfyldte QC-kriterier
26. marts 2007
Først opslået (Skøn)
27. marts 2007
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
25. august 2017
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
24. august 2017
Sidst verificeret
1. august 2017
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Luftvejssygdomme
- Neoplasmer
- Lungesygdomme
- Neoplasmer efter sted
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Lungeneoplasmer
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antimetabolitter
- Antineoplastiske midler
- Antikolesteræmiske midler
- Hypolipidæmiske midler
- Lipidregulerende midler
- Hydroxymethylglutaryl-CoA-reduktasehæmmere
- Proteinkinasehæmmere
- Gefitinib
- Simvastatin
Andre undersøgelses-id-numre
- NCCCTS-06-177
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
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