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Surgery With or Without Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer
This study is ongoing, but not recruiting participants.
First Received: November 6, 2000   Last Updated: July 10, 2009   History of Changes
Sponsor: European Organization for Research and Treatment of Cancer
Collaborators: Australasian Gastro-Intestinal Trials Group
Arbeitsgruppe Lebermetastasen und Tumoren
Cancer Research UK
Fondation Francaise de Cancerologie Digestive
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006479
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: FOLFOX regimen
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
Procedure: adjuvant therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Phase III

Study Type: Interventional
Study Design: Treatment
Official Title: Pre- and Post-Operative Chemotherapy With Oxaliplatin 5FU/LV Versus Surgery Alone in Resectable Liver Metastases From Colorectal Origin - Phase III Study

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: September 2000
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006479

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

Additional Information:
Publications:
Benoist S, Nordlinger B. The Role of Preoperative Chemotherapy in Patients with Resectable Colorectal Liver Metastases. Ann Surg Oncol. 2009 Jun 25; [Epub ahead of print]
Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007-16.
Julie C, Lutz MP, Aust D, et al.: Pathological analysis of hepatic injury after oxaliplatin-based neoadjuvant chemotherapy of colorectal cancer liver metastases: results of the EORTC Intergroup phase III study 40983. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-241, 2007.
Nordlinger B, Sorbye H, Collette L, et al.: Final results of the EORTC Intergroup randomized phase III study 40983 [EPOC] evaluating the benefit of peri-operative FOLFOX4 chemotherapy for patients with potentially resectable colorectal cancer liver metastases. [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA5, 2007.
Gruenberger T, Sorbye H, Debois M, et al.: Tumor response to pre-operative chemotherapy (CT) with FOLFOX-4 for resectable colorectal cancer liver metastases (LM). Interim results of EORTC Intergroup randomized phase III study 40983. [Abstract] J Clin Oncol 24 (Suppl 18): A-3500, 2006.
Nordlinger B, Sorbye H, Debois M, et al.: Feasibility and risks of pre-operative chemotherapy (CT) with Folfox 4 and surgery for resectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983. [Abstract] J Clin Oncol 23 (Suppl 16): A-3528, 253s, 2005.

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
Study First Received: November 6, 2000
Last Updated: July 10, 2009
ClinicalTrials.gov Identifier: NCT00006479     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
liver metastases

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Colonic Diseases
Leucovorin
Rectal Diseases
Neoplastic Processes
Oxaliplatin
Neoplasms by Site
Pathologic Processes
Vitamins
Therapeutic Uses
Neoplasm Metastasis
Micronutrients
Vitamin B Complex
Digestive System Neoplasms
Growth Substances
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on November 22, 2009