- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT01027676
Study of Vorinostat and Gefitinib in Relapsed/ or Refractory Patients With Advanced Non-small Cell Carcinoma (NSCLC)
13. november 2013 oppdatert av: Ji-youn Han, National Cancer Center, Korea
Phase I/II Study of Vorinostat and Gefitinib in Relapsed/ or Refractory Patients With Advanced Non-small Cell Carcinoma (NSCLC)
Gefitinib is an orally active epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) and produces 8-20% of response rates in patients with advanced non-small cell lung cancer (NSCLC).
Vorinostat (suberoylanilide hydroxamic acid [SAHA]) is a small-molecule inhibitor of histone deacetylase (HDAC) and induces cell differentiation, cell cycle arrest, and apoptosis in several tumor cells.
There is a strong synergistic antiproliferative effect of vorinostat in combination with gefitinib in NSCLC cells.
Vorinostat increases expression of E-cadherin and ErbB-3, which results in increased sensitivity to gefitinib.
Moreover, In-vitro studies have shown that vorinostat leads to acetylation and disruption of Hsp90, which may lead to decreases in activity of pro-growth and prosurvival client proteins (J Bio Chem 2005;280:26729, Br J Cancer 2006;95:S2).
These findings suggest that combination of vorinostat with gefitinib may improve the efficacy of gefitinib in NSCLC.
Studieoversikt
Status
Ukjent
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Phase I design
- Three patients will be treated per cohort for one cycle (28 days per cycle).
- If no DLTs are recorded, treatment will continue and three patients will be treated in the subsequent cohort.
- However, if a patient develops a DLT, another three patients will be treated in this cohort for one cycle.
- If there are no more DLTs, dose escalation continues.
- If more than one of three patients develop a DLT in any cohort, another three patients will be treated in the next lower dosage cohort.
- If no DLTs are recorded in any of the cohorts, cohort 3 will be expanded to six patients.
- Up to 12 patients will be enrolled at the MTD.
- The phase II dose for this combined treatment will be therefore defined as the highest dosage cohort in which six patients had been treated and there are less than three DLTs.
Studietype
Intervensjonell
Registrering (Forventet)
50
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Gyeonggi-do
-
Goyang-si, Gyeonggi-do, Korea, Republikken, 410-769
- National Cancer Center
-
-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
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 28 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 0-2 on the ECOG criteria.
- At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1)
- Estimated life expectancy of at least 8 weeks.
- Patient compliance that allow adequate follow-up.
- Adequate hematologic (WBC count 4,000/mm3, 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.
- 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: but patient could be enrolled, if they have recovered from any treatment-related toxicities NCI CTCAE grade ≤2
- Inability to swallow tablets
- Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence).
- More than three previous chemotherapy regimens for NSCLC
- Previous treatment with any EGFR-TKI
- Patients who have been exposed to any prior HDAC inhibitor, with the exception of exception of valpronic acid used for treating seizures, provided there is a 30-day washout period
- Patients with active HIV or hepatitis B or C infection
- Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, cyclosporine A, valpronic acid, Phenobarbital, ketoconazole, coumarin-derivative anticoagulants 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 postobstructive pneumonia
- Major surgery other than biopsy within the past two weeks.
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Eksperimentell: study arm
single arm Gefitinib plus vorinostat
|
Gefitinib 250mg/QD plus vorinostat D1~7 & D15-21 / QD q 4weeks
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Progression-Free Survival
Tidsramme: every 8 weeks
|
The first day of treatment to the date that disease progression is reported or death date
|
every 8 weeks
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Overall Survival
Tidsramme: every 8 weeks
|
The first day of treatment to the date that death is reported or last survival status reported or
|
every 8 weeks
|
Objective Response rate
Tidsramme: every 8 weeks
|
The date of first evaluation to the date of disease progression
|
every 8 weeks
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: JI-YOUN HAN, M.D., National Cancer Center
Publikasjoner og nyttige lenker
Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart
1. juni 2010
Primær fullføring (Forventet)
1. desember 2013
Studiet fullført (Forventet)
1. mars 2014
Datoer for studieregistrering
Først innsendt
8. desember 2009
Først innsendt som oppfylte QC-kriteriene
8. desember 2009
Først lagt ut (Anslag)
9. desember 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
14. november 2013
Siste oppdatering sendt inn som oppfylte QC-kriteriene
13. november 2013
Sist bekreftet
1. november 2013
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- NCCCTS-09-433
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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