- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT00482222
Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer
A Prospective Randomised Open Label Trial of Oxaliplatin/Fluoropyrimidine Versus Oxaliplatin/Fluoropyrimidine Plus Cetuximab Pre and Post Operatively in Patients With Resectable Colorectal Liver Metastasis Requiring Chemotherapy
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy together with monoclonal antibodies before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without cetuximab in treating liver metastases caused by colorectal cancer.
PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without cetuximab before and after surgery in treating patients with resectable liver metastases caused by colorectal cancer.
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
- Arzneimittel: Fluorouracil
- Arzneimittel: Leucovorin-Calcium
- Verfahren: adjuvante Therapie
- Verfahren: neoadjuvante Therapie
- Arzneimittel: Oxaliplatin
- Verfahren: Bewertung der Lebensqualität
- Arzneimittel: Capecitabin
- Sonstiges: Untersuchung sozioökonomischer und demographischer Variablen
- Biologisch: Cetuximab
Detaillierte Beschreibung
OBJECTIVES:
Primary
- Compare progression-free survival of patients with resectable colorectal liver metastases treated with neoadjuvant and adjuvant combination chemotherapy with vs without cetuximab.
Secondary
- Compare the overall survival of patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
- Compare the cost effectiveness of these regimens in these patients.
OUTLINE: This is a prospective, randomized, multicenter, open-label study. Patients are stratified according to participating center and assigned chemotherapy regimen. Patients are randomized to 1 of 2 treatment arms.
Neoadjuvant therapy:
Arm I: Patients receive 1 of the following chemotherapy regimens:
- OxMdG: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX: Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive 1 of the following regimens:
- OxMdG + cetuximab: Patients receive cetuximab IV over 1-2 hours on day 1 and OxMdG chemotherapy as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- CAPOX + cetuximab: Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and CAPOX chemotherapy as in arm I. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Surgery: Beginning 2-6 weeks after completion of chemotherapy, patients in both arms undergo liver resection.
Adjuvant therapy: Beginning 4-8 weeks after completion of surgery, patients receive treatment (OxMdG or CAPOX with or without cetuximab) as in arm I or II of neoadjuvant therapy.
- Arm I: Treatment with OxMdG repeats every 2 weeks for up to 6 courses and treatment with CAPOX repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Treatment with OxMdG + cetuximab repeats every 2 weeks for up to 6 courses and treatment with CAPOX + cetuximab repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 12 weeks during chemotherapy, at completion of study treatment, every 3 months for 1 year, and then every 6 months thereafter.
Cost per life year and per quality-adjusted life year is assessed at baseline, every 12 weeks during treatment, and then at 3, 5, and 10 years.
After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Studientyp
Einschreibung (Voraussichtlich)
Phase
- Phase 3
Kontakte und Standorte
Studienorte
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England
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Basildon, England, Vereinigtes Königreich, SS16 5NL
- Rekrutierung
- Basildon University Hospital
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Kontakt:
- Pauline Leonard, MD
- Telefonnummer: 44-1702-435-555
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Basingstoke, England, Vereinigtes Königreich, RG24 9NA
- Rekrutierung
- Basingstoke and North Hampshire NHS Foundation Trust
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Kontakt:
- Charlotte Rees, MD
- Telefonnummer: 44-125-631-4793
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Bournemouth, England, Vereinigtes Königreich, BH7 7DW
- Rekrutierung
- Royal Bournemouth Hospital
-
Kontakt:
- Tamas Hickish, MD
- Telefonnummer: 44-1202-303-626
- E-Mail: tamas.hickish@rbch.nhs.uk
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Cambridge, England, Vereinigtes Königreich, CB2 0QQ
- Rekrutierung
- Addenbrooke's Hospital
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Kontakt:
- Pippa Corrie, PhD, FRCP
- Telefonnummer: 44-1223-274-401
- E-Mail: pippa.corrie@addenbrookes.nhs.uk
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Guildford, England, Vereinigtes Königreich, GU2 7XX
- Rekrutierung
- St. Luke's Cancer Centre at Royal Surrey County Hospital
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Kontakt:
- Sharadah Essapen, MD
- Telefonnummer: 44-1483-571-122
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Liverpool, England, Vereinigtes Königreich, L9 7AL
- Rekrutierung
- Aintree University Hospital
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Kontakt:
- Graeme J. Poston, MD
- Telefonnummer: 44-151-525-5980
- E-Mail: graeme.poston@aintree.nhs.uk
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Liverpool, England, Vereinigtes Königreich, L9 7AL
- Rekrutierung
- Royal Liverpool University Hospital
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Kontakt:
- Paula Ghaneh, MD
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London, England, Vereinigtes Königreich, SW3 6JJ
- Rekrutierung
- Royal Marsden - London
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Kontakt:
- David Cunningham, MD
- Telefonnummer: 44-20-8661-3156
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London, England, Vereinigtes Königreich, EC1A 7BE
- Rekrutierung
- Saint Bartholomew's Hospital
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London, England, Vereinigtes Königreich, W6 8RF
- Rekrutierung
- Charing Cross Hospital
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Kontakt:
- Charles P. Lowdell, MD, BSc, MBBS, FRCP, FRCR
- Telefonnummer: 44-208-383-0576
- E-Mail: charles.lowdell@imperial.nhs.uk
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London, England, Vereinigtes Königreich, NW3 2PF
- Rekrutierung
- UCL Cancer Institute
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Kontakt:
- Astrid Mayer, MD
- Telefonnummer: 44-207-794-0500
- E-Mail: a.mayer@ucl.ac.uk
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Merseyside, England, Vereinigtes Königreich, CH63 4JY
- Rekrutierung
- Clatterbridge Centre For Oncology
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Newport, England, Vereinigtes Königreich, PO30 5TG
- Rekrutierung
- St. Mary's Hospital
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Kontakt:
- Christopher Baughan, MD
- Telefonnummer: 44-1983-524-081
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Nottingham, England, Vereinigtes Königreich, NG5 1PB
- Rekrutierung
- Cancer Research Centre at Weston Park Hospital
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Kontakt:
- J. Hornbuckle, MD
- Telefonnummer: 44-115-969-1169 ext. 47599
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Poole Dorset, England, Vereinigtes Königreich, BH15 2JB
- Rekrutierung
- Dorset Cancer Centre
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Kontakt:
- Tamas Hickish, MD
- Telefonnummer: 44-1202-442-532
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Salisbury, England, Vereinigtes Königreich, SP2 8BJ
- Rekrutierung
- Salisbury District Hospital
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Southampton, England, Vereinigtes Königreich, SO16 6YD
- Rekrutierung
- Southampton General Hospital
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Kontakt:
- John N. Primrose, MD
- Telefonnummer: 44-23-8079-6144
- E-Mail: j.n.primrose@soton.ac.uk
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Sutton, England, Vereinigtes Königreich, SM2 5PT
- Rekrutierung
- Royal Marsden - Surrey
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Westcliff-On-Sea, England, Vereinigtes Königreich, SS0 0RY
- Rekrutierung
- Southend University Hospital NHS Foundation Trust
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Kontakt:
- Pauline Leonard, MD
- Telefonnummer: 44-1702-435-555
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Worthing, England, Vereinigtes Königreich, BN11 2DH
- Rekrutierung
- Worthing Hospital
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Kontakt:
- Andrew Webb, MD
- Telefonnummer: 44-1903-205-111
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Wales
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Cardiff, Wales, Vereinigtes Königreich, CF14 2TL
- Rekrutierung
- Velindre Cancer Center at Velindre Hospital
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Kontakt:
- Timothy Maughan, MD
- Telefonnummer: 44-2920-316-904
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Cardiff, Wales, Vereinigtes Königreich, CF14 4XW
- Rekrutierung
- University Hospital of Wales
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Kontakt:
- Timothy Maughan, MD
- Telefonnummer: 44-2920-316-904
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
DISEASE CHARACTERISTICS:
Histologically* or radiologically confirmed primary adenocarcinoma of the colon or rectum
- Advanced and/or metastatic disease NOTE: *Liver metastases should not be biopsied
Must have potentially resectable liver metastases present, as defined by any of the following:
- Metachronous metastases AND complete resection of the primary tumor without gross or microscopic evidence of residual disease (R0)
- Synchronous metastases AND R0 resection of the primary tumor > 1 month before study entry
- Synchronous metastases with sufficient evidence (e.g., by CT scan or diagnostic laparoscopy) that both the primary tumor and the liver metastases can be completely resected during the same procedure and resection of primary tumor can be delayed for 3-4 months
- Suboptimally resectable disease (i.e., potentially resectable disease with compromise of the resection margins)
- No detectable extrahepatic tumor that cannot be completely resected
- Unidimensionally measurable disease
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- WBC ≥ 4,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count > 150,000/mm³
- Bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 3 times ULN
- Creatinine clearance > 50 mL/min OR glomerular filtration rate > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No psychiatric or neurological condition that would preclude study compliance
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No other prior or concurrent malignant disease that, in the opinion of the investigator, would preclude study treatment
- No concurrent severe uncontrolled medical illness (including poorly-controlled angina or myocardial infarction within the past 3 months) that would preclude study treatment
- No known hypersensitivity reaction to any of the components of the study drugs
PRIOR CONCURRENT THERAPY:
- No prior systemic chemotherapy for metastatic disease
- More than 6 months since prior adjuvant chemotherapy comprising fluorouracil, leucovorin calcium, capecitabine, or irinotecan hydrochloride
- More than 1 month since prior rectal chemoradiotherapy comprising fluorouracil and leucovorin calcium
- No concurrent contraindicated medication
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Aktiver Komparator: OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
|
|
Experimental: OxMdG / IrMdG chemotherapy with cetuximab
OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Progression-free survival
Zeitfenster: end of study
|
end of study
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
Gesamtüberleben
Zeitfenster: Ende des Studiums
|
Ende des Studiums
|
Response rate before surgery as assessed by RECIST criteria
Zeitfenster: end of study
|
end of study
|
Pathological resection status
Zeitfenster: end of study
|
end of study
|
Toxicity
Zeitfenster: end of study
|
end of study
|
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
Zeitfenster: end of study
|
end of study
|
Cost effectiveness
Zeitfenster: end of study
|
end of study
|
Safety
Zeitfenster: end of study
|
end of study
|
Mitarbeiter und Ermittler
Sponsor
Ermittler
- Studienstuhl: John N. Primrose, MD, University Hospital Southampton Nhs Foundation Trust
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- Pathologische Prozesse
- Neubildungen
- Neubildungen nach Standort
- Gastrointestinale Neubildungen
- Neoplasmen des Verdauungssystems
- Magen-Darm-Erkrankungen
- Darmerkrankungen
- Darmerkrankungen
- Darmtumoren
- Rektale Erkrankungen
- Neoplastische Prozesse
- Kolorektale Neubildungen
- Neoplasma Metastasierung
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antimetaboliten, antineoplastisch
- Antimetaboliten
- Antineoplastische Mittel
- Immunsuppressive Mittel
- Immunologische Faktoren
- Schutzmittel
- Antineoplastische Mittel, immunologische
- Mikronährstoffe
- Vitamine
- Calciumregulierende Hormone und Wirkstoffe
- Gegenmittel
- Vitamin B-Komplex
- Fluorouracil
- Capecitabin
- Oxaliplatin
- Leucovorin
- Kalzium
- Levoleucovorin
- Cetuximab
Andere Studien-ID-Nummern
- CDR0000549541
- USCTU-4351
- USCTU-EPOC
- EUDRACT-2006-003121-82
- ISRCTN22944367
- EU-20732
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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