Combination Chemotherapy and Cetuximab as First-Line Therapy in Treating Patients With Advanced and/or Metastatic Colorectal Cancer
15 settembre 2021 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
169
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Nicosia, Cipro
- Bank Of Cyprus Oncology Centre
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Bath, Regno Unito
- Royal United Hospital
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Bournemouth, Regno Unito
- Royal Bournemouth Hospital
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Cambridge, Regno Unito
- Addenbrookes Hospital
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Dartford, Regno Unito
- Darent Valley Hospital
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Hereford, Regno Unito
- Hereford County Hospital
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London, Regno Unito
- Charing Cross Hospital
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London, Regno Unito
- Guys and St Thomas' Hospitals
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Poole, Regno Unito
- Dorset Cancer Centre, Poole Hospital
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Sheffield, Regno Unito, S10 2SJ
- Weston Park
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Southport, Regno Unito
- Southport and Ormskirk
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St Helens, Regno Unito
- St Helens and Whiston hospitals
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Warrington, Regno Unito
- Warrington and Halton Hospitals
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Worcester, Regno Unito
- Worcestershire Royal Hospital
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England
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Bradford, England, Regno Unito, BD9 6RJ
- Bradford Royal Infirmary
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Cheltenham, England, Regno Unito, GL53 7AN
- Gloucestershire Oncology Centre at Cheltenham General Hospital
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Colchester, England, Regno Unito, C03 3NB
- Essex County Hospital
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Dorchester, England, Regno Unito, DT1 2JY
- Dorset County Hospital
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Guildford, England, Regno Unito, GU2 7XX
- St. Luke's Cancer Centre at Royal Surrey County Hospital
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London, England, Regno Unito, W12 OHS
- Hammersmith Hospital
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London, England, Regno Unito, W2 1NY
- St. Mary's Hospital
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Oxford, England, Regno Unito, OX3 7LJ
- Churchill Hospital
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Peterborough, England, Regno Unito, PE3 6DA
- Peterborough Hospitals Trust
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Stoke-On-Trent, England, Regno Unito, ST4 7LN
- University Hospital of North Staffordshire
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Wales
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Swansea, Wales, Regno Unito, SA2 8QA
- Singleton Hospital
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 100 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore attivo: 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
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Sperimentale: 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
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
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Failure-free survival at 10 months
Lasso di tempo: 10 months
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10 months
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
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Safety of cetuximab reintroduction, in terms of risk of grade 3-4 allergic reactions
Lasso di tempo: 12, 24 and 36 weeks
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12, 24 and 36 weeks
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Proportion of patients achieving disease control (complete response plus partial response plus stable disease) at 24 weeks
Lasso di tempo: 24 weeks
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24 weeks
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Overall survival
Lasso di tempo: at 12, 24 and 36 weeks
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at 12, 24 and 36 weeks
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Progression-free survival
Lasso di tempo: at 12, 24 and 36 weeks
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at 12, 24 and 36 weeks
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Response rates
Lasso di tempo: at 12, 24 and 36 weeks
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at 12, 24 and 36 weeks
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Toxicity of each treatment regimen by NCI CTCAE v3.0
Lasso di tempo: at 12, 24 and 36 weeks
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at 12, 24 and 36 weeks
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Investigatore principale: Harpreet S. Wasan, Hammersmith Hospitals NHS Trust
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 luglio 2007
Completamento primario (Effettivo)
1 giugno 2010
Completamento dello studio (Effettivo)
1 settembre 2015
Date di iscrizione allo studio
Primo inviato
19 marzo 2008
Primo inviato che soddisfa i criteri di controllo qualità
19 marzo 2008
Primo Inserito (Stima)
20 marzo 2008
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
22 settembre 2021
Ultimo aggiornamento inviato che soddisfa i criteri QC
15 settembre 2021
Ultimo verificato
1 settembre 2021
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie dell'apparato digerente
- Neoplasie
- Neoplasie per sede
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie gastrointestinali
- Malattie del colon
- Malattie intestinali
- Neoplasie intestinali
- Malattie del retto
- Neoplasie colorettali
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti protettivi
- Agenti antineoplastici, immunologici
- Micronutrienti
- Vitamine
- Ormoni e agenti regolatori del calcio
- Antidoti
- Complesso di vitamina B
- Fluorouracile
- Capecitabina
- Oxaliplatino
- Leucovorin
- Calcio
- Levoleucovorin
- Cetuximab
Altri numeri di identificazione dello studio
- CDR0000589635
- MRC-CTU-COIN-B/CR11
- EUDRACT:2006-003049-17
- ISRCTN38375681
- EU-20828
- MERCK-MRC-CTU-COIN-B/CR11
Piano per i dati dei singoli partecipanti (IPD)
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Descrizione del piano IPD
Publication
Dati/documenti di studio
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .