Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer
15. September 2021 aktualisiert von: Cheryl Pugh
A Two-arm Phase II Randomised Trial of Intermittent Chemotherapy Plus Continuous Cetuximab and of Intermittent Chemotherapy Plus Intermittent Cetuximab in First Line Treatment of Patients With K-ras-normal (Wild-type) Metastatic Colorectal Cancer
RATIONALE: Drugs used in chemotherapy 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. It is not yet known whether giving combination chemotherapy together with intermittent cetuximab is more effective than combination chemotherapy given together with continuous cetuximab in treating colorectal cancer.
PURPOSE: This randomized phase II trial is studying giving combination chemotherapy together with intermittent cetuximab to see how well it works compared to combination chemotherapy given together with continuous cetuximab as first-line therapy in treating patients with advanced or metastatic colorectal cancer.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Detaillierte Beschreibung
OBJECTIVES:
Primary
- To compare the activity, in terms of failure-free survival, of patients with K-ras-normal (wild type) advanced and/or metastatic colorectal cancer treated with intermittent combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil (OxMdG) or oxaliplatin and capecitabine (XELOX) and intermittent vs continuous cetuximab as first-line therapy.
- To compare the safety and feasibility of these regimens in these patients.
Secondary
- To compare the safety of cetuximab reintroduction, in terms of frequency of grade 3-4 allergic reactions in these patients.
- To compare improvement in disease control (i.e., complete response plus partial response plus stable disease) at 24 weeks in patients treated with these regimens.
- To compare overall and progression-free survival of patients treated with these regimens.
- To compare response rates at 12, 24, and 36 weeks in patients treated with these regimens.
- To compare toxicity of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are randomised to 1 of 2 treatment arms.
Arm I (intermittent chemotherapy and intermittent cetuximab): Patients receive 1 of the following combination chemotherapy and cetuximab regimens:
- OxMdG: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14 days for up to 6 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
- XELOX (for patients with line-related problems): Patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15 (28 doses). Patients also receive cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses (12 weeks) in the absence of disease progression or unacceptable toxicity.
After completion of 12 weeks of study therapy, patients with disease progression are removed from study. Patients with stable or responding disease stop treatment with OxMdG or XELOX and cetuximab and undergo clinical evaluation at least every 6 weeks until disease progression or clinical deterioration. Upon evidence of disease progression or clinical deterioration, patients restart treatment with OxMdG or XELOX and cetuximab as before and continue to alternate 12 weeks of treatment with treatment breaks in the absence of disease progression or unacceptable toxicity. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy or best supportive care.
- Arm II (intermittent chemotherapy and continuous cetuximab): Patients receive OxMdG or XELOX and cetuximab for 12 weeks as in arm I. Patients with disease progression after 12 weeks of study therapy are removed from study. Patients with stable or responding disease* after 12 weeks of study therapy stop treatment with OxMdG or XELOX and continue treatment with cetuximab weekly as monotherapy in the absence of disease progression or unacceptable toxicity. Patients undergo clinical evaluation as in arm I. Upon progression, patients restart treatment with OxMdG or XELOX and continue cetuximab, as before, alternating 12 weeks of combined OxMdG or XELOX and cetuximab therapy with cetuximab monotherapy. Patients with disease progression during study therapy stop treatment and proceed to second-line therapy as in arm I.
Previously collected tumor tissue samples are obtained at baseline and analyzed by IHC for EGFR status of tumor.
After completion of study treatment, patients are followed every 12 weeks.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
169
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
-
Bath, Vereinigtes Königreich
- Royal United Hospital
-
Bournemouth, Vereinigtes Königreich
- Royal Bournemouth Hospital
-
Cambridge, Vereinigtes Königreich
- Addenbrookes Hospital
-
Dartford, Vereinigtes Königreich
- Darent Valley Hospital
-
Hereford, Vereinigtes Königreich
- Hereford County Hospital
-
London, Vereinigtes Königreich
- Charing Cross Hospital
-
London, Vereinigtes Königreich
- Guys and St Thomas' Hospitals
-
Poole, Vereinigtes Königreich
- Dorset Cancer Centre, Poole Hospital
-
Sheffield, Vereinigtes Königreich, S10 2SJ
- Weston Park
-
Southport, Vereinigtes Königreich
- Southport and Ormskirk
-
St Helens, Vereinigtes Königreich
- St Helens and Whiston hospitals
-
Warrington, Vereinigtes Königreich
- Warrington and Halton Hospitals
-
Worcester, Vereinigtes Königreich
- Worcestershire Royal Hospital
-
-
England
-
Bradford, England, Vereinigtes Königreich, BD9 6RJ
- Bradford Royal Infirmary
-
Cheltenham, England, Vereinigtes Königreich, GL53 7AN
- Gloucestershire Oncology Centre at Cheltenham General Hospital
-
Colchester, England, Vereinigtes Königreich, C03 3NB
- Essex County Hospital
-
Dorchester, England, Vereinigtes Königreich, DT1 2JY
- Dorset County Hospital
-
Guildford, England, Vereinigtes Königreich, GU2 7XX
- St. Luke's Cancer Centre at Royal Surrey County Hospital
-
London, England, Vereinigtes Königreich, W12 OHS
- Hammersmith Hospital
-
London, England, Vereinigtes Königreich, W2 1NY
- St. Mary's Hospital
-
Oxford, England, Vereinigtes Königreich, OX3 7LJ
- Churchill Hospital
-
Peterborough, England, Vereinigtes Königreich, PE3 6DA
- Peterborough Hospitals Trust
-
Stoke-On-Trent, England, Vereinigtes Königreich, ST4 7LN
- University Hospital of North Staffordshire
-
-
Wales
-
Swansea, Wales, Vereinigtes Königreich, SA2 8QA
- Singleton Hospital
-
-
-
-
-
Nicosia, Zypern
- Bank Of Cyprus Oncology Centre
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 100 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
DISEASE CHARACTERISTICS:
Diagnosis of colorectal adenocarcinoma, defined by 1 of the following:
- Prior or current histologically confirmed primary adenocarcinoma of colon or rectum with clinical or radiological evidence of advanced and/or metastatic disease
- Histologically and cytologically confirmed metastatic adenocarcinoma with clinical and/or radiological evidence of colorectal primary tumor
- Unidimensionally measurable disease by RECIST criteria
Inoperable metastatic or locoregional disease
Potentially resectable liver metastases allowed provided the following criteria are met:
- Fewer than 4 unilobar liver metastases, each < 4 cm in size and without major vascular involvement
- No combination chemotherapy allowed prior to the planned resection of operable liver metastases
- No confirmed K-ras mutation of tumor after screening
- No brain metastases
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Must be considered fit to undergo combination chemotherapy
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Serum bilirubin ≤ 1.25 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 5 times ULN
- AST or ALT ≤ 2.5 times ULN
- Creatinine clearance ≥ 50mL/min OR glomerular filtration rate ≥ 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No severe uncontrolled concurrent medical illness (including poorly controlled angina or myocardial infarction within the past 12 weeks) likely to interfere with protocol treatments
- No psychiatric or neurological condition that would preclude study compliance with oral medication or giving informed consent
- No partial or complete bowel obstruction
- No preexisting neuropathy > grade 1
- No prior or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with COIN-B treatment or assessment of response
- No patients with known hypersensitivity reactions to any of the components of the study treatments
- No proven dihydropyrimidine dehydrogenase deficiency (DPD) or personal or family history of DPD
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior systemic palliative chemotherapy for metastatic disease
- No prior oxaliplatin
- More than 1 month since prior adjuvant chemotherapy comprising fluorouracil (with or without leucovorin calcium), capecitabine, or irinotecan hydrochloride
- More than 1 month since prior chemoradiotherapy comprising fluorouracil (with or without leucovorin calcium) or capecitabine for rectal cancer
- No ongoing requirement for contraindicated concurrent medication
- No concurrent enrollment in any type of study other than observational studies
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
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: D
Intermittent chemotherapy plus intermittent cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period off all therapy, with reintroduction of the same chemotherapy and cetuximab regimen for a further 12 weeks after initial progression off treatment
|
|
|
Experimental: E
Intermittent chemotherapy plus continuous cetuximab treatment comprising 12 weeks of chemotherapy plus cetuximab followed by a period of withdrawal of the chemotherapy, but continued weekly cetuximab monotherapy (maintenance cetuximab), with reintroduction of the same chemotherapy regimen to the cetuximab for a further 12 weeks after initial progression off chemotherapy treatment
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Failure-free survival at 10 months
Zeitfenster: 10 months
|
10 months
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions
Zeitfenster: 12, 24 and 36 weeks
|
12, 24 and 36 weeks
|
|
Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks
Zeitfenster: 24 weeks
|
24 weeks
|
|
Overall survival
Zeitfenster: at 12, 24 and 36 weeks
|
at 12, 24 and 36 weeks
|
|
Progression-free survival
Zeitfenster: at 12, 24 and 36 weeks
|
at 12, 24 and 36 weeks
|
|
Response rates
Zeitfenster: at 12, 24 and 36 weeks
|
at 12, 24 and 36 weeks
|
|
Toxicity of each treatment regimen by NCI CTCAE v3.0
Zeitfenster: at 12, 24 and 36 weeks
|
at 12, 24 and 36 weeks
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Ermittler
- Hauptermittler: Harpreet S. Wasan, Hammersmith Hospitals NHS Trust
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Nützliche Links
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. Juli 2007
Primärer Abschluss (Tatsächlich)
1. Juni 2010
Studienabschluss (Tatsächlich)
1. September 2015
Studienanmeldedaten
Zuerst eingereicht
19. März 2008
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
19. März 2008
Zuerst gepostet (Schätzen)
20. März 2008
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
22. September 2021
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
15. September 2021
Zuletzt verifiziert
1. September 2021
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Verdauungssystems
- Neubildungen
- Neubildungen nach Standort
- Gastrointestinale Neubildungen
- Neoplasmen des Verdauungssystems
- Magen-Darm-Erkrankungen
- Darmerkrankungen
- Darmerkrankungen
- Darmtumoren
- Rektale Erkrankungen
- Kolorektale Neubildungen
- 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
- CDR0000589635
- MRC-CTU-COIN-B/CR11
- EUDRACT:2006-003049-17
- ISRCTN38375681
- EU-20828
- MERCK-MRC-CTU-COIN-B/CR11
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
JA
Beschreibung des IPD-Plans
Publication
Studiendaten/Dokumente
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 .