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

NCT00006479 | Unknown Phase 3

• 8 other identifiers: CDR0000068309EORTC-40983AGITG-EORTC-40983ALM-CAO-EORTC-40983CRUK-LON-EORTC-40983FFCD-EORTC-40983EU-20048CRC-EORTC-40983
• Study Type: interventional
• Target: N/A
• Locations: 12 countries
• Sites: 109

Brief Summary

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.

Conditions

Colorectal Cancer; Metastatic Cancer

Keywords

stage IV colon cancer; stage IV rectal cancer; recurrent colon cancer; recurrent rectal cancer; liver metastases

Interventions

FOLFOX regimen DRUG

fluorouracil DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

adjuvant therapy PROCEDURE

conventional surgery PROCEDURE

neoadjuvant therapy PROCEDURE

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Australasian Gastro-Intestinal Trials Group: collaborator
• Arbeitsgruppe Lebermetastasen und Tumoren: collaborator
• Cancer Research UK: collaborator
• Fondation Francaise de Cancerologie Digestive: collaborator

Study Sites (111)

Bankstown - Lidcombe Hospital

Bankstown, New South Wales, NSW 2200, Australia

Location

Institute of Oncology at Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Newcastle Mater Misericordiae Hospital

Waratah, New South Wales, 2298, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Ashford Cancer Centre

Ashford, South Australia, 5035, Australia

Location

Flinder Medical Centres

Bedford Park, South Australia, 5042, Australia

Location

Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Austin and Repatriation Medical Centre

Heidelberg West, Victoria, 3081, Australia

Location

Mount Hospital

Perth, Western Australia, 6000, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Sir Charles Gairdner Hospital - Perth

Perth, Western Australia, 6009, Australia

Location

Allgemeines Krankenhaus der Stadt Wien

Vienna, A-1090, Austria

Location

Kaiser Franz Josef Hospital

Vienna, A-1100, Austria

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, 1090, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, B-9000, Belgium

Location

Hopital de Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

Cazk Groeninghe - Campus St-Niklaas

Kortrijk, B-8500, Belgium

Location

U.Z. Gasthuisberg

Leuven, B-3000, Belgium

Location

Centre Hospitalier - Abbeville

Abbeville, 80101, France

Location

Centre Hospitalier Regional et Universitaire d'Angers

Angers, 49033, France

Location

C.H.G. Beauvais

Beauvais, 60021, France

Location

CHR de Besancon - Hopital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHU Ambroise Pare

Boulogne-Billancourt, F-92104, France

Location

C.H. Bourg En Bresse

Bourg-en-Bresse, 01012, France

Location

CMC Bligny

Briis-sous-Forges, 91640, France

Location

CHU de Caen

Caen, 14033, France

Location

Hopital Louis Pasteur

Colmar, 68024, France

Location

Centre Hospitalier Universitaire Henri Mondor

Créteil, 94010, France

Location

Hopital Du Bocage

Dijon, 21034, France

Location

CHU de Grenoble - Hopital de la Tronche

Grenoble, 38043, France

Location

Centre Hospitalier Departemental

La Roche-sur-Yon, F-85025, France

Location

Clinique Du Pre

Le Mans, F-72018, France

Location

Hopital Robert Boulin

Libourne, 33500, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

CHU de la Timone

Marseille, 13385, France

Location

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, 34298, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Hopital Cochin

Paris, 75674, France

Location

C.H.G. De Pau

Pau, 64000, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Hopital Charles Nicolle

Rouen, 76031, France

Location

Hopital Universitaire Hautepierre

Strasbourg, 67098, France

Location

Centre Hospitalier Regional de Purpan

Toulouse, 31059, France

Location

CHU de Tours

Tours, 37044, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Hopital Paul Brousse

Villejuif, 94804, France

Location

Helios Klinikum Berlin

Berlin, 13125, Germany

Location

Robert Roessle Klinik at Charite - Campus Berlin Buch im Helios Klinikum Berlin

Berlin, D-13122, Germany

Location

Staedtisches Klinikum Dessau

Dessau, D-06822, Germany

Location

Medizinische Klinik I

Dresden, D-01307, Germany

Location

Department of Medicine III

Erlangen, D-91054, Germany

Location

Kliniken Essen - Mitte

Essen, D-45136, Germany

Location

Klinikum der J.W. Goethe Universitaet

Frankfurt, D-60590, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, D-79106, Germany

Location

Klinik der Justus - Leibig - Universitaet Giessen

Giessen, D-35385, Germany

Location

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, D-07740, Germany

Location

Knappschaft Krankenhaus

Langendreer, D-44892, Germany

Location

Universitaet Leipzig

Leipzig, D-04103, Germany

Location

Staedtisches Klinikum Leipzig

Leipzig, D-04129, Germany

Location

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, D-39120, Germany

Location

Johannes Gutenberg University

Mainz, D-55101, Germany

Location

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, D-81675, Germany

Location

Klinikum der Universitaet Regensburg

Regensburg, D-93053, Germany

Location

Caritasklinik St. Theresia

Saarbrücken, D-66113, Germany

Location

Eberhard Karls Universitaet

Tübingen, D-72076, Germany

Location

Dr. Horst-Schmidt-Kliniken

Wiesbaden, D-65199, Germany

Location

Universitaets-Hautklinik Wuerzburg

Würzburg, D-97080, Germany

Location

Prince of Wales Hospital

Shatin, N.T., Hong Kong

Location

Ospedale San Martino/Cliniche Universitarie Convenzionate

Genoa (Genova), 16132, Italy

Location

Universita di Padova

Padua, 35128, Italy

Location

Leiden University Medical Center

Leiden, 2300 CA, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Christchurch Hospital

Christchurch, 1, New Zealand

Location

Haukeland Hospital - University of Bergen

Bergen, N-5021, Norway

Location

Instituto Portugues de Oncologia Centro do Porto, SA

Porto, 4200-072, Portugal

Location

Sahlgrenska University Hospital

Gothenburg (Goteborg), S-413 45, Sweden

Location

Karolinska University Hospital/Huddinge

Stockholm, S-171 76, Sweden

Location

Uppsala University Hospital

Uppsala, S-75185, Sweden

Location

North Hampshire Hospital

Basingstoke, England, RG24 9NA, United Kingdom

Location

Queen Elizabeth Hospital at University of Birmingham

Birmingham, England, B15 2TH, United Kingdom

Location

Bristol Haematology and Oncology Centre

Bristol, England, BS2 8ED, United Kingdom

Location

Bristol Royal Infirmary

Bristol, England, BS2 8HW, United Kingdom

Location

Addenbrooke's NHS Trust

Cambridge, England, CB2 2QQ, United Kingdom

Location

St. Luke's Cancer Center

Guildford, England, GU2 5XX, United Kingdom

Location

Cookridge Hospital at Leeds Teaching Hospital NHS Trust

Leeds, England, LS16 6QB, United Kingdom

Location

St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, England, LE1 5WW, United Kingdom

Location

Royal Liverpool and Broadgreen Hospitals

Liverpool, England, L7 8XP, United Kingdom

Location

Royal London Hospital

London, England, E1 1BB, United Kingdom

Location

Royal Free Hospital

London, England, NW3 2QG, United Kingdom

Location

St. George's Hospital

London, England, SW17 0QT, United Kingdom

Location

Clatterbridge Centre for Oncology NHS Trust

Merseyside, England, CH63 4JY, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

Location

Mount Vernon Hospital

Northwood, England, HA6 2RN, United Kingdom

Location

Queen's Medical Centre

Nottingham, England, NG7 2UH, United Kingdom

Location

Royal Preston Hospital

Preston, England, PR2 9HT, United Kingdom

Location

Weston Park Hospital

Sheffield, England, S1O 2SJ, United Kingdom

Location

Royal South Hants Hospital

Southampton, England, SO14 0YG, United Kingdom

Location

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Royal Infirmary of Edinburgh at Little France

Edinburgh, Scotland, EH3 9YW, United Kingdom

Location

Ysbyty Gwynedd

Bangor, Wales, LL57 2PW, United Kingdom

Location

North Manchester Healthcare NHS Trust

Manchester, M8 6RB, United Kingdom

Location

Related Publications (11)

• Sorbye H, Mauer M, Gruenberger T, et al.: Predictive factors for the effect of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC phase III study 40983). [Abstract] J Clin Oncol 28 (Suppl 15): A-3544, 2010.

  RESULT

• Sorbye H, Mauer M, Gruenberger T, et al.: Evaluation of carcinoembryonic antigen (CEA) as a predictive baseline factor for the benefit of perioperative FOLFOX in resectable liver metastasis from colorectal cancer (EORTC study 40983). [Abstract] American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium, 22-24 January 2010, Orlando, Florida. A-407, 2010.

  RESULT

• Benoist S, Nordlinger B. The role of preoperative chemotherapy in patients with resectable colorectal liver metastases. Ann Surg Oncol. 2009 Sep;16(9):2385-90. doi: 10.1245/s10434-009-0492-7. Epub 2009 Jun 25.

  PMID: 19554377 RESULT

• 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); Federation Francophone de Cancerologie 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. doi: 10.1016/S0140-6736(08)60455-9.

  PMID: 18358928 RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• 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.

  RESULT

• Tanis E, Julie C, Emile JF, Mauer M, Nordlinger B, Aust D, Roth A, Lutz MP, Gruenberger T, Wrba F, Sorbye H, Bechstein W, Schlag P, Fisseler A, Ruers T. Prognostic impact of immune response in resectable colorectal liver metastases treated by surgery alone or surgery with perioperative FOLFOX in the randomised EORTC study 40983. Eur J Cancer. 2015 Nov;51(17):2708-17. doi: 10.1016/j.ejca.2015.08.014. Epub 2015 Sep 2.

  PMID: 26342674 DERIVED

• 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, Mauer M, Tanis E, 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); Federation Francophone de Cancerologie Digestive (FFCD). Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. doi: 10.1016/S1470-2045(13)70447-9. Epub 2013 Oct 11.

  PMID: 24120480 DERIVED

• Sorbye H, Mauer M, Gruenberger T, 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, Van Cutsem E, Scheithauer W, Lutz MP, Nordlinger B; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK (CRUK); Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Federation Francophone de Cancerologie Digestive (FFCD). Predictive factors for the benefit of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC Intergroup Trial 40983). Ann Surg. 2012 Mar;255(3):534-9. doi: 10.1097/SLA.0b013e3182456aa2.

  PMID: 22314329 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin; Chemotherapy, Adjuvant; Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Bernard Nordlinger, MD

  Hopital Ambroise Pare

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NETWORK

Study Record Dates

• First Submitted: November 6, 2000
• First Posted: January 27, 2003
• Study Start: September 1, 2000
• Last Updated: April 18, 2011

Record last verified: 2000-12

Locations

AU (15); NL (2); NZ (1); IT (2); BE (7); FR (31); DE (21); NO (1); PT (1); SE (3); GB (24); HK (1)