- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00824785
REAL3 Trial of Efficacy of EOX With/Without Panitumumab in Previously Untreated Adv OG Cancer (REAL3)
10. desember 2012 oppdatert av: Professor David Cunningham, Royal Marsden NHS Foundation Trust
REAL 3 : A Randomised Open-labelled Multicentre Trial of the Efficacy of Epirubicin, Oxaliplatin and Capecitabine (EOX) With or Without Panitumumab in Previously Untreated Advanced Oesophago-gastric Cancer
To determine whether adding panitumumab, an antibody against the epidermal growth factor receptor (EGFR), to standard chemotherapy with epirubicin, oxaliplatin and capecitabine (EOX), improves the duration of survival of patients with advanced stomach and oesophageal cancer.
Studieoversikt
Status
Avsluttet
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Multicentre phase III, open labelled, randomised controlled trial.
Randomisation will be 1:1 Arm A EOX and Arm B EOX + panitumumab.
There will be a pilot phase II study of which the first 200 patients will be randomised and the primary endpoint for interim analysis will be when these patients have completed 6 months follow-up
Studietype
Intervensjonell
Registrering (Faktiske)
574
Fase
- Fase 3
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
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Bournemouth, Storbritannia
- Bournemouth
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Guildford, Storbritannia
- St Luke's Guildford
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Liverpool, Storbritannia
- Royal Liverpool
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London, Storbritannia, SW3 6JJ
- Royal Marsden NHS Foundation Trust
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Newcastle, Storbritannia
- Newcastle
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Sutton, Storbritannia
- Royal Marsden NHS Foundation Trust
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Wirral, Storbritannia
- Clatterbridge Oncology Centre
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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:
- Histologically verified inoperable locally advanced or metastatic adenocarcinoma or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction, or stomach.
- Slides of tumour tissue should be available for centralised EGFR staining
- Uni-dimensionally measurable disease (CT or MRI as per RECIST).
- No prior chemotherapy including previous adjuvant chemotherapy
- No prior radiotherapy including adjuvant radiotherapy. Patients receiving palliative radiotherapy to sites of disease that are not measurable may be eligible and should be discussed with the Chief Investigator.
- Male/female patients aged ≥18 years.
- WHO Performance status 0, 1 or 2.
- Patients should have a projected life expectancy of at least 3 months.
- Completion of baseline quality of life questionnaire (EORTC QLQ C30).
- Adequate cardiac function; formal measurement of left ventricular ejection fraction is only required if clinically indicated.
- Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion).
- Adequate renal function: calculated creatinine clearance ≥50ml/minute.
- Adequate liver function: serum bilirubin ≤1.5x ULN; ALT/AST ≤2.5x ULN; ALP ≤3x ULN (in the absence of liver metastases). If liver metastases are present, serum transaminases ≤5x ULN are permitted.
- Written informed consent must be obtained from the patient before any study-specific procedures are performed (see Section 12.0).
Note: Epidermal growth factor receptor (EGFR) positivity by immunohistochemistry will not be required for study entry. Slides obtained from previously collected paraffin embedded archived specimens will be collected centrally for EGFR staining. A multivariate analysis will then be performed to exclude any effects of EGFR status on outcome measures
Exclusion Criteria:
- Tumours of squamous histology.
- Patients with locally advanced oesophageal cancer suitable for definitive chemoradiotherapy.
- Documented or symptomatic brain metastases and/or central nervous system metastases or leptomeningeal disease.
- Previous chemotherapy or radiotherapy. See Inclusion criteria for note regarding palliative radiotherapy.
- Any major surgery within 4 weeks prior to the start of study treatment.
- Any prior treatment with an EGFR signal transduction directed therapy.
- Treatment with non-permitted medication.
- Clinically significant (i.e. active) cardiac disease e.g. symptomatic coronary artery disease, uncontrolled cardiac dysrhythmia, or myocardial infarction within the last 12 months. Patients with any history of clinically significant cardiac failure are excluded from study entry.
- History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan.
- Known peripheral neuropathy >Grade 1 (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible).
- Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication (administration of capecitabine by naso-gastric or jejunostomy feeding tube is permitted).
- Known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Known hypersensitivity to panitumumab, components of the EOX regimen, or any of the constituents of these agents.
- Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection.
- Other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial.
- Female patients who may be pregnant or breastfeeding. Potential female patients of childbearing potential must have a negative pregnancy test within 7 days prior to randomisation, or have had amenorrhea for more than 2 years.
- Patients of child-bearing potential not consenting to use adequate contraceptive precautions or abstinence during the course of the study and for 6 months after the last study drug administration for females, and 1 month for males.
- Any other malignancies within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix).
- Treatment with another investigational agent within 30 days of commencing study treatment.
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: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
Aktiv komparator: Arm A EOX
EOX chemotherapy (epirubicin, oxaliplatin and capecitabine)
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epirubicin 50mg/m(2) IV on day 1 oxaliplatin 130mg/m(2) IV on day 1 with hydration capecitabine 1250mg/m(2)/day PO in two divided doses continuously from days 1-21
|
Aktiv komparator: Arm B EOX + panitumumab.
EOX chemotherapy with the addition of panitumumab 9mg/kg every 21 days
|
epirubicin 50mg/m(2) IV on day 1 oxaliplatin 100mg/m(2) IV on day 1 with hydration capecitabine 1000mg/m(2)/day PO in two divided doses continuously from days 1-21 panitumumab -9 mg/kg every 21 days
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
Overall survival
Tidsramme: Early termination
|
Study closed early due to lack of efficacy
|
Early termination
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
---|---|---|
response rate, toxicity, quality of life and PFS
Tidsramme: Early termination
|
Study closed early due to lack of efficacy
|
Early termination
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Etterforskere
- Hovedetterforsker: Prof Cunningham, David, Royal Marsden NHS Foundation Trust
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.
Generelle publikasjoner
- Smyth EC, Vlachogiannis G, Hedayat S, Harbery A, Hulkki-Wilson S, Salati M, Kouvelakis K, Fernandez-Mateos J, Cresswell GD, Fontana E, Seidlitz T, Peckitt C, Hahne JC, Lampis A, Begum R, Watkins D, Rao S, Starling N, Waddell T, Okines A, Crosby T, Mansoor W, Wadsley J, Middleton G, Fassan M, Wotherspoon A, Braconi C, Chau I, Vivanco I, Sottoriva A, Stange DE, Cunningham D, Valeri N. EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers. Gut. 2021 Sep;70(9):1632-1641. doi: 10.1136/gutjnl-2020-322658. Epub 2020 Nov 16.
- Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. doi: 10.1016/S1470-2045(13)70096-2. Epub 2013 Apr 15. Erratum In: Lancet Oncol. 2013 Jun;14(7):e254. Frances, Alicia [corrected to Okines, Alicia Frances Clare].
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. mai 2008
Primær fullføring (Forventet)
1. februar 2013
Studiet fullført (Forventet)
1. februar 2013
Datoer for studieregistrering
Først innsendt
16. januar 2009
Først innsendt som oppfylte QC-kriteriene
16. januar 2009
Først lagt ut (Anslag)
19. januar 2009
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
11. desember 2012
Siste oppdatering sendt inn som oppfylte QC-kriteriene
10. desember 2012
Sist bekreftet
1. desember 2012
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Sykdommer i fordøyelsessystemet
- Neoplasmer
- Neoplasmer etter nettsted
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Magesykdommer
- Neoplasmer i magen
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antimetabolitter, antineoplastisk
- Antimetabolitter
- Antineoplastiske midler
- Topoisomerase II-hemmere
- Topoisomerasehemmere
- Antineoplastiske midler, immunologiske
- Antibiotika, antineoplastisk
- Capecitabin
- Epirubicin
- Oksaliplatin
- Panitumumab
Andre studie-ID-numre
- CCR3024
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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