Surgery With or Without Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

April 15, 2011 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Pre- and Post-Operative Chemotherapy With Oxaliplatin 5FU/LV Versus Surgery Alone in Resectable Liver Metastases From Colorectal Origin - Phase III Study

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with surgery may kill more tumor cells. It is not yet known if surgery is more effective with or without chemotherapy for liver metastases.

PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have liver metastases from colorectal cancer.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the progression-free and overall survival of patients with resectable colorectal liver metastases treated with surgery with or without neoadjuvant and adjuvant oxaliplatin, fluorouracil, and leucovorin calcium.
  • Compare the percentage of patients with total resection with these two treatments.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, prior adjuvant chemotherapy (yes vs no), plasma CEA level in ng/mL at diagnosis of liver metastases (5 or less vs 6 to 30 vs 31 or greater), serosa extension of primary cancer (absent T1 or T2 vs present T3 or T4), lymphatic spread of primary cancer (absent vs present N+), time interval between diagnosis of primary tumor to metastases (2 years or more vs fewer than 2 years), and number of metastases (1 to 3 vs 4). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium (LV) IV over 2 hours followed by fluorouracil (5-FU) IV over 22 hours on days 1 and 2. Treatment repeats every 15 days for 6 courses in the absence of disease progression or unacceptable toxicity.

At 2 to 5 weeks after chemotherapy, patients undergo liver resection. Patients with progressive disease after 3 courses of chemotherapy undergo liver resection at least 2 weeks after completion of course 3 and do not receive postoperative chemotherapy.

At 2 to 5 weeks after surgery, patients receive oxaliplatin, LV, and 5-FU as in preoperative chemotherapy.

  • Arm II: Patients undergo liver resection. Patients are followed every 3 months for 2 years and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 330 patients (165 per arm) will be accrued for this study within 3 years.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Bankstown, New South Wales, Australia, NSW 2200
        • Bankstown - Lidcombe Hospital
      • Randwick, New South Wales, Australia, 2031
        • Institute of Oncology at Prince of Wales Hospital
      • St. Leonards, New South Wales, Australia, 2065
        • Royal North Shore Hospital
      • Waratah, New South Wales, Australia, 2298
        • Newcastle Mater Misericordiae Hospital
    • Queensland
      • Brisbane, Queensland, Australia, 4102
        • Princess Alexandra Hospital
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
    • South Australia
      • Ashford, South Australia, Australia, 5035
        • Ashford Cancer Centre
      • Bedford Park, South Australia, Australia, 5042
        • Flinder Medical Centres
      • Woodville, South Australia, Australia, 5011
        • Queen Elizabeth Hospital
    • Tasmania
      • Launceston, Tasmania, Australia, 7250
        • Launceston General Hospital
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Frankston Hospital
      • Heidelberg West, Victoria, Australia, 3081
        • Austin and Repatriation Medical Centre
    • Western Australia
      • Perth, Western Australia, Australia, 6000
        • Royal Perth Hospital
      • Perth, Western Australia, Australia, 6000
        • Mount Hospital
      • Perth, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital - Perth
  • Austria
      • Vienna, Austria, A-1090
        • Allgemeines Krankenhaus Der Stadt Wien
      • Vienna, Austria, A-1100
        • Kaiser Franz Josef Hospital
  • Belgium
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Brussels, Belgium, 1070
        • Hopital Universitaire Erasme
      • Brussels, Belgium, 1090
        • Academisch Ziekenhuis der Vrije Universiteit Brussel
      • Ghent, Belgium, B-9000
        • Universitair Ziekenhuis Gent
      • Haine Saint Paul, Belgium, 7100
        • Hopital de Jolimont
      • Kortrijk, Belgium, B-8500
        • Cazk Groeninghe - Campus St-Niklaas
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • France
      • Abbeville, France, 80101
        • Centre Hospitalier - Abbeville
      • Angers, France, 49033
        • Centre Hospitalier Regional et Universitaire d'Angers
      • Beauvais, France, 60021
        • C.H.G. Beauvais
      • Besancon, France, 25030
        • CHR de Besancon - Hopital Jean Minjoz
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Boulogne Billancourt, France, F-92104
        • CHU Ambroise Pare
      • Bourg En Bresse, France, 01012
        • C.H. Bourg En Bresse
      • Briis Sous Forges, France, 91640
        • CMC Bligny
      • Caen, France, 14033
        • CHU de Caen
      • Colmar, France, 68024
        • Hôpital Louis Pasteur
      • Creteil, France, 94010
        • Centre Hospitalier Universitaire Henri Mondor
      • Dijon, France, 21034
        • Hopital Du Bocage
      • Grenoble, France, 38043
        • CHU de Grenoble - Hopital de la Tronche
      • La Roche Sur Yon, France, F-85025
        • Centre Hospitalier departemental
      • Le Mans, France, F-72018
        • Clinique du Pré
      • Libourne, France, 33500
        • Hôpital Robert Boulin
      • Limoges, France, 87042
        • Centre Hospital Regional Universitaire de Limoges
      • Marseille, France, 13385
        • CHU de la Timone
      • Montpellier, France, 34298
        • Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
      • Paris, France, 75015
        • Hopital Europeen Georges Pompidou
      • Paris, France, 75674
        • Hopital Cochin
      • Paris, France, 75010
        • Hopital Lariboisiere
      • Pau, France, 64000
        • C.H.G. De Pau
      • Pessac, France, 33604
        • Hôpital Haut Lévêque
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Rouen, France, 76031
        • Hopital Charles Nicolle
      • Strasbourg, France, 67098
        • Hopital Universitaire Hautepierre
      • Toulouse, France, 31059
        • Centre Hospitalier Regional de Purpan
      • Tours, France, 37044
        • CHU de Tours
      • Vandoeuvre-les-Nancy, France, 54511
        • Centre Alexis Vautrin
      • Villejuif, France, 94804
        • Hopital Paul Brousse
  • Germany
      • Berlin, Germany, 13125
        • Helios Klinikum Berlin
      • Berlin, Germany, D-13122
        • Robert Roessle Klinik at Charite - Campus Berlin Buch im Helios Klinikum Berlin
      • Bochum-Langendreer, Germany, D-44892
        • Knappschaft Krankenhaus
      • Dessau, Germany, D-06822
        • Staedtisches Klinikum Dessau
      • Dresden, Germany, D-01307
        • Medizinische Klinik I
      • Erlangen, Germany, D-91054
        • Department of Medicine III
      • Essen, Germany, D-45136
        • Kliniken Essen - Mitte
      • Frankfurt, Germany, D-60590
        • Klinikum der J.W. Goethe Universitaet
      • Freiburg, Germany, D-79106
        • Universitaetsklinikum Freiburg
      • Giessen, Germany, D-35385
        • Klinik der Justus - Leibig - Universitaet Giessen
      • Jena, Germany, D-07740
        • Klinikum der Friedrich-Schiller Universitaet Jena
      • Leipzig, Germany, D-04103
        • Universitaet Leipzig
      • Leipzig, Germany, D-04129
        • Staedtisches Klinikum Leipzig
      • Magdeburg, Germany, D-39120
        • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
      • Mainz, Germany, D-55101
        • Johannes Gutenberg University
      • Munich, Germany, D-81675
        • Klinikum Rechts der Isar - Technische Universitaet Muenchen
      • Regensburg, Germany, D-93053
        • Klinikum der Universitaet Regensburg
      • Saarbrucken, Germany, D-66113
        • Caritasklinik St. Theresia
      • Tuebingen, Germany, D-72076
        • Eberhard Karls Universitaet
      • Wiesbaden, Germany, D-65199
        • Dr. Horst-Schmidt-Kliniken
      • Wuerzburg, Germany, D-97080
        • Universitaets-Hautklinik Wuerzburg
  • Hong Kong
      • Shatin, N.T., Hong Kong
        • Prince of Wales Hospital
  • Italy
      • Genoa (Genova), Italy, 16132
        • Ospedale San Martino/Cliniche Universitarie Convenzionate
      • Padova, Italy, 35128
        • Universita di Padova
  • Netherlands
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Maastricht, Netherlands, 6202 AZ
        • Academisch Ziekenhuis Maastricht
  • New Zealand
      • Christchurch, New Zealand, 1
        • Christchurch Hospital
  • Norway
      • Bergen, Norway, N-5021
        • Haukeland Hospital - University of Bergen
  • Portugal
      • Porto, Portugal, 4200-072
        • Instituto Portugues de Oncologia Centro do Porto, SA
  • Sweden
      • Gothenburg (Goteborg), Sweden, S-413 45
        • Sahlgrenska University Hospital
      • Stockholm, Sweden, S-171 76
        • Karolinska University Hospital/Huddinge
      • Uppsala, Sweden, S-75185
        • Uppsala University Hospital
  • United Kingdom
      • Manchester, United Kingdom, M8 6RB
        • North Manchester Healthcare NHS Trust
    • England
      • Basingstoke, England, United Kingdom, RG24 9NA
        • North Hampshire Hospital
      • Birmingham, England, United Kingdom, B15 2TH
        • Queen Elizabeth Hospital at University of Birmingham
      • Bristol, England, United Kingdom, BS2 8ED
        • Bristol Haematology and Oncology Centre
      • Bristol, England, United Kingdom, BS2 8HW
        • Bristol Royal Infirmary
      • Cambridge, England, United Kingdom, CB2 2QQ
        • Addenbrooke's NHS Trust
      • Guildford, England, United Kingdom, GU2 5XX
        • St. Luke's Cancer Center
      • Leeds, England, United Kingdom, LS9 7TF
        • St. James's University Hospital
      • Leeds, England, United Kingdom, LS16 6QB
        • Cookridge Hospital at Leeds Teaching Hospital NHS Trust
      • Leicester, England, United Kingdom, LE1 5WW
        • Leicester Royal Infirmary
      • Liverpool, England, United Kingdom, L7 8XP
        • Royal Liverpool and Broadgreen Hospitals
      • London, England, United Kingdom, E1 1BB
        • Royal London Hospital
      • London, England, United Kingdom, NW3 2QG
        • Royal Free Hospital
      • London, England, United Kingdom, SW17 0QT
        • St. George's Hospital
      • Merseyside, England, United Kingdom, CH63 4JY
        • Clatterbridge Centre for Oncology NHS Trust
      • Newcastle-Upon-Tyne, England, United Kingdom, NE7 7DN
        • Freeman Hospital
      • Northwood, England, United Kingdom, HA6 2RN
        • Mount Vernon Hospital
      • Nottingham, England, United Kingdom, NG7 2UH
        • Queen's Medical Centre
      • Preston, England, United Kingdom, PR2 9HT
        • Royal Preston Hospital
      • Sheffield, England, United Kingdom, S1O 2SJ
        • Weston Park Hospital
      • Southampton, England, United Kingdom, SO16 6YD
        • Southampton General Hospital
      • Southampton, England, United Kingdom, SO14 0YG
        • Royal South Hants Hospital
    • Scotland
      • Edinburgh, Scotland, United Kingdom, EH3 9YW
        • Royal Infirmary of Edinburgh at Little France
    • Wales
      • Bangor, Wales, United Kingdom, LL57 2PW
        • Ysbyty Gwynedd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of potentially resectable colorectal liver metastases that meets one of the following criteria:

    • Metachronous metastases after complete resection of primary tumor without gross or microscopic evidence of residual disease
    • Synchronous metastases after complete resection of primary tumor more than 1 month before study
    • Synchronous metastases with sufficient evidence (i.e., CAT scan or diagnostic laparoscopy) that both the primary tumor and liver metastases can be completely resected during the same procedure and resection of primary may be delayed 3-4 months

PATIENT CHARACTERISTICS:

Age:

  • 18 to 80

Performance status:

  • WHO 0-2
  • Karnofsky 60-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • No hepatic insufficiency

Renal:

  • Creatinine less than 2 times upper limit of normal

Cardiovascular:

  • No uncontrolled congestive heart failure or angina pectoris
  • No hypertension or arrhythmia

Other:

  • No other malignancy within the past 10 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No peripheral neuropathy greater than grade 1
  • No prior significant neurologic or psychiatric disorders
  • No active infection
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No concurrent biologic therapy

Chemotherapy:

  • No prior chemotherapy for advanced disease
  • Prior adjuvant chemotherapy for primary cancer allowed unless included oxaliplatin
  • No other concurrent chemotherapy

Endocrine therapy:

  • No concurrent anticancer endocrine therapy

Radiotherapy:

  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics

Other:

  • At least 30 days since prior investigational drugs
  • No concurrent investigational drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Cancer Research UK
Australasian Gastro-Intestinal Trials Group
Arbeitsgruppe Lebermetastasen und Tumoren
Fondation Francaise de Cancerologie Digestive

Investigators

  • Bernard Nordlinger, MD, Hopital Ambroise Pare
  • Study Chair: Euan T. Walpole, MD, Princess Alexandra Hospital
  • Study Chair: Wolf O. Bechstein, MD, Arbeitsgruppe Lebermetastasen und Tumoren
  • Study Chair: John N. Primrose, MD, University Hospital Southampton NHS Foundation Trust
  • Study Chair: Philippe Rougier, MD, Hopital Ambroise Pare

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2000

Primary Completion

December 7, 2022

Study Completion

December 7, 2022

Study Registration Dates

First Submitted

November 6, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

April 18, 2011

Last Update Submitted That Met QC Criteria

April 15, 2011

Last Verified

December 1, 2000

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068309
  • EORTC-40983
  • AGITG-EORTC-40983
  • ALM-CAO-EORTC-40983
  • CRUK-LON-EORTC-40983
  • FFCD-EORTC-40983
  • EU-20048
  • CRC-EORTC-40983

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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