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Combination Chemotherapy With or Without Cetuximab Before and After Surgery in Treating Patients With Resectable Liver Metastases Caused By Colorectal Cancer

22. januar 2013 opdateret af: University of Southampton

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.

Studieoversigt

Status

Ukendt

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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

Undersøgelsestype

Interventionel

Tilmelding (Forventet)

340

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Det Forenede Kongerige
    • England
      • Basildon, England, Det Forenede Kongerige, SS16 5NL
        • Rekruttering
        • Basildon University Hospital
        • Kontakt:
          • Pauline Leonard, MD
          • Telefonnummer: 44-1702-435-555
      • Basingstoke, England, Det Forenede Kongerige, RG24 9NA
        • Rekruttering
        • Basingstoke and North Hampshire NHS Foundation Trust
        • Kontakt:
          • Charlotte Rees, MD
          • Telefonnummer: 44-125-631-4793
      • Bournemouth, England, Det Forenede Kongerige, BH7 7DW
        • Rekruttering
        • Royal Bournemouth Hospital
        • Kontakt:
      • Cambridge, England, Det Forenede Kongerige, CB2 0QQ
      • Guildford, England, Det Forenede Kongerige, GU2 7XX
        • Rekruttering
        • St. Luke's Cancer Centre at Royal Surrey County Hospital
        • Kontakt:
          • Sharadah Essapen, MD
          • Telefonnummer: 44-1483-571-122
      • Liverpool, England, Det Forenede Kongerige, L9 7AL
        • Rekruttering
        • Aintree University Hospital
        • Kontakt:
      • Liverpool, England, Det Forenede Kongerige, L9 7AL
        • Rekruttering
        • Royal Liverpool University Hospital
        • Kontakt:
          • Paula Ghaneh, MD
      • London, England, Det Forenede Kongerige, SW3 6JJ
        • Rekruttering
        • Royal Marsden - London
        • Kontakt:
          • David Cunningham, MD
          • Telefonnummer: 44-20-8661-3156
      • London, England, Det Forenede Kongerige, EC1A 7BE
        • Rekruttering
        • Saint Bartholomew's Hospital
      • London, England, Det Forenede Kongerige, W6 8RF
        • Rekruttering
        • Charing Cross Hospital
        • Kontakt:
      • London, England, Det Forenede Kongerige, NW3 2PF
        • Rekruttering
        • UCL Cancer Institute
        • Kontakt:
      • Merseyside, England, Det Forenede Kongerige, CH63 4JY
        • Rekruttering
        • Clatterbridge Centre for Oncology
      • Newport, England, Det Forenede Kongerige, PO30 5TG
        • Rekruttering
        • St. Mary's Hospital
        • Kontakt:
          • Christopher Baughan, MD
          • Telefonnummer: 44-1983-524-081
      • Nottingham, England, Det Forenede Kongerige, NG5 1PB
        • Rekruttering
        • Cancer Research Centre at Weston Park Hospital
        • Kontakt:
          • J. Hornbuckle, MD
          • Telefonnummer: 44-115-969-1169 ext. 47599
      • Poole Dorset, England, Det Forenede Kongerige, BH15 2JB
        • Rekruttering
        • Dorset Cancer Centre
        • Kontakt:
          • Tamas Hickish, MD
          • Telefonnummer: 44-1202-442-532
      • Salisbury, England, Det Forenede Kongerige, SP2 8BJ
        • Rekruttering
        • Salisbury District Hospital
      • Southampton, England, Det Forenede Kongerige, SO16 6YD
        • Rekruttering
        • Southampton General Hospital
        • Kontakt:
      • Sutton, England, Det Forenede Kongerige, SM2 5PT
        • Rekruttering
        • Royal Marsden - Surrey
      • Westcliff-On-Sea, England, Det Forenede Kongerige, SS0 0RY
        • Rekruttering
        • Southend University Hospital NHS Foundation Trust
        • Kontakt:
          • Pauline Leonard, MD
          • Telefonnummer: 44-1702-435-555
      • Worthing, England, Det Forenede Kongerige, BN11 2DH
        • Rekruttering
        • Worthing Hospital
        • Kontakt:
          • Andrew Webb, MD
          • Telefonnummer: 44-1903-205-111
    • Wales
      • Cardiff, Wales, Det Forenede Kongerige, CF14 2TL
        • Rekruttering
        • Velindre Cancer Center at Velindre Hospital
        • Kontakt:
          • Timothy Maughan, MD
          • Telefonnummer: 44-2920-316-904
      • Cardiff, Wales, Det Forenede Kongerige, CF14 4XW
        • Rekruttering
        • University Hospital of Wales
        • Kontakt:
          • Timothy Maughan, MD
          • Telefonnummer: 44-2920-316-904

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Aktiv komparator: OxMdG / IrMdG chemotherapy
OxMdG / IrMdG chemotherapy for 12 weeks Followed by surgery OxMdG / IrMdG chemotherapy for 12 weeks
Medicin: fluorouracil
Medicin: leucovorin calcium
Procedure: adjuverende terapi
Procedure: neoadjuverende terapi
Medicin: oxaliplatin
Procedure: livskvalitetsvurdering
Medicin: capecitabin
Andet: undersøgelse af socioøkonomiske og demografiske variabler
Eksperimentel: OxMdG / IrMdG chemotherapy with cetuximab
OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks Followed by Surgery OxMdG / IrMdG chemotherapy with cetuximab for 12 weeks
Medicin: fluorouracil
Medicin: leucovorin calcium
Procedure: adjuverende terapi
Procedure: neoadjuverende terapi
Medicin: oxaliplatin
Procedure: livskvalitetsvurdering
Medicin: capecitabin
Andet: undersøgelse af socioøkonomiske og demografiske variabler
Biologisk: cetuximab

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Progression-free survival
Tidsramme: end of study
end of study

Sekundære resultatmål

Resultatmål
Tidsramme
Samlet overlevelse
Tidsramme: afslutning på studiet
afslutning på studiet
Response rate before surgery as assessed by RECIST criteria
Tidsramme: end of study
end of study
Pathological resection status
Tidsramme: end of study
end of study
Toxicity
Tidsramme: end of study
end of study
Quality of life as assessed by the EQ-5D, EORTC QLQ-C30, and EORTC QLQ-LMC21
Tidsramme: end of study
end of study
Cost effectiveness
Tidsramme: end of study
end of study
Safety
Tidsramme: end of study
end of study

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

University of Southampton

Samarbejdspartnere

University Hospital Southampton NHS Foundation Trust

Efterforskere

  • Studiestol: John N. Primrose, MD, University Hospital Southampton NHS Foundation Trust

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. februar 2007

Primær færdiggørelse (Forventet)

1. december 2014

Datoer for studieregistrering

Først indsendt

4. juni 2007

Først indsendt, der opfyldte QC-kriterier

4. juni 2007

Først opslået (Skøn)

5. juni 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

23. januar 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

22. januar 2013

Sidst verificeret

1. april 2008

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CDR0000549541
  • USCTU-4351
  • USCTU-EPOC
  • EUDRACT-2006-003121-82
  • ISRCTN22944367
  • EU-20732

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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