AzTrials
AzTrials

Colorectal CancerPhase 3NCT00006479

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

A Phase 3 study testing FOLFOX regimen, fluorouracil and leucovorin calcium in people with Colorectal Cancer and Metastatic Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 111 sites in 13 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Colorectal Cancer, Metastatic Cancer
What is being tested?
FOLFOX regimen, fluorouracil and leucovorin calcium
Type of treatment
Surgery or procedure
How many people
Not given
Where
111 sitesin 13 countries
Study dates
Sep 2000to not given
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

111 sites in 13 countries.

111 sites in 13 countries

France31 sites

  • Centre Hospitalier - Abbeville

    Abbeville, 80101

  • Centre Hospitalier Regional et Universitaire d'Angers

    Angers, 49033

  • C.H.G. Beauvais

    Beauvais, 60021

  • CHR de Besancon - Hopital Jean Minjoz

    Besançon, 25030

  • Institut Bergonie

    Bordeaux, 33076

  • CHU Ambroise Pare

    Boulogne-Billancourt, F-92104

  • C.H. Bourg En Bresse

    Bourg-en-Bresse, 01012

  • CMC Bligny

    Briis-sous-Forges, 91640

  • CHU de Caen

    Caen, 14033

  • Hopital Louis Pasteur

    Colmar, 68024

  • Centre Hospitalier Universitaire Henri Mondor

    Créteil, 94010

  • Hopital Du Bocage

    Dijon, 21034

  • CHU de Grenoble - Hopital de la Tronche

    Grenoble, 38043

  • Centre Hospitalier Departemental

    La Roche-sur-Yon, F-85025

  • Clinique Du Pre

    Le Mans, F-72018

  • Hopital Robert Boulin

    Libourne, 33500

  • Centre Hospital Regional Universitaire de Limoges

    Limoges, 87042

  • CHU de la Timone

    Marseille, 13385

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

    Montpellier, 34298

  • Hopital Lariboisiere

    Paris, 75010

  • Hopital Europeen Georges Pompidou

    Paris, 75015

  • Hopital Cochin

    Paris, 75674

  • C.H.G. De Pau

    Pau, 64000

  • Hopital Haut Leveque

    Pessac, 33604

  • Centre Eugene Marquis

    Rennes, 35042

  • Hopital Charles Nicolle

    Rouen, 76031

  • Hopital Universitaire Hautepierre

    Strasbourg, 67098

  • Centre Hospitalier Regional de Purpan

    Toulouse, 31059

  • CHU de Tours

    Tours, 37044

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

  • Hopital Paul Brousse

    Villejuif, 94804

Other trials in France

United Kingdom24 sites

  • Ysbyty Gwynedd

    Bangor, Wales, LL57 2PW

  • North Hampshire Hospital

    Basingstoke, England, RG24 9NA

  • Queen Elizabeth Hospital at University of Birmingham

    Birmingham, England, B15 2TH

  • Bristol Haematology and Oncology Centre

    Bristol, England, BS2 8ED

  • Bristol Royal Infirmary

    Bristol, England, BS2 8HW

  • Addenbrooke's NHS Trust

    Cambridge, England, CB2 2QQ

  • Royal Infirmary of Edinburgh at Little France

    Edinburgh, Scotland, EH3 9YW

  • St. Luke's Cancer Center

    Guildford, England, GU2 5XX

  • Cookridge Hospital at Leeds Teaching Hospital NHS Trust

    Leeds, England, LS16 6QB

  • St. James's University Hospital

    Leeds, England, LS9 7TF

  • Leicester Royal Infirmary

    Leicester, England, LE1 5WW

  • Royal Liverpool and Broadgreen Hospitals

    Liverpool, England, L7 8XP

  • Royal London Hospital

    London, England, E1 1BB

  • Royal Free Hospital

    London, England, NW3 2QG

  • St. George's Hospital

    London, England, SW17 0QT

  • North Manchester Healthcare NHS Trust

    Manchester, M8 6RB

  • Clatterbridge Centre for Oncology NHS Trust

    Merseyside, England, CH63 4JY

  • Freeman Hospital

    Newcastle upon Tyne, England, NE7 7DN

  • Mount Vernon Hospital

    Northwood, England, HA6 2RN

  • Queen's Medical Centre

    Nottingham, England, NG7 2UH

  • Royal Preston Hospital

    Preston, England, PR2 9HT

  • Weston Park Hospital

    Sheffield, England, S1O 2SJ

  • Royal South Hants Hospital

    Southampton, England, SO14 0YG

  • Southampton General Hospital

    Southampton, England, SO16 6YD

Other trials in United Kingdom

Germany21 sites

  • Helios Klinikum Berlin

    Berlin, 13125

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

    Berlin, D-13122

  • Staedtisches Klinikum Dessau

    Dessau, D-06822

  • Medizinische Klinik I

    Dresden, D-01307

  • Department of Medicine III

    Erlangen, D-91054

  • Kliniken Essen - Mitte

    Essen, D-45136

  • Klinikum der J.W. Goethe Universitaet

    Frankfurt, D-60590

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, D-79106

  • Klinik der Justus - Leibig - Universitaet Giessen

    Giessen, D-35385

  • Klinikum der Friedrich-Schiller Universitaet Jena

    Jena, D-07740

  • Knappschaft Krankenhaus

    Langendreer, D-44892

  • Universitaet Leipzig

    Leipzig, D-04103

  • Staedtisches Klinikum Leipzig

    Leipzig, D-04129

  • Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

    Magdeburg, D-39120

  • Johannes Gutenberg University

    Mainz, D-55101

  • Klinikum Rechts Der Isar - Technische Universitaet Muenchen

    Munich, D-81675

  • Klinikum der Universitaet Regensburg

    Regensburg, D-93053

  • Caritasklinik St. Theresia

    Saarbrücken, D-66113

  • Eberhard Karls Universitaet

    Tübingen, D-72076

  • Dr. Horst-Schmidt-Kliniken

    Wiesbaden, D-65199

  • Universitaets-Hautklinik Wuerzburg

    Würzburg, D-97080

Other trials in Germany

Australia15 sites

  • Ashford Cancer Centre

    Ashford, South Australia, 5035

  • Bankstown - Lidcombe Hospital

    Bankstown, New South Wales, NSW 2200

  • Flinder Medical Centres

    Bedford Park, South Australia, 5042

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland, 4029

  • Princess Alexandra Hospital

    Brisbane, Queensland, 4102

  • Frankston Hospital

    Frankston, Victoria, 3199

  • Austin and Repatriation Medical Centre

    Heidelberg West, Victoria, 3081

  • Launceston General Hospital

    Launceston, Tasmania, 7250

  • Mount Hospital

    Perth, Western Australia, 6000

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Sir Charles Gairdner Hospital - Perth

    Perth, Western Australia, 6009

  • Institute of Oncology at Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Royal North Shore Hospital

    St Leonards, New South Wales, 2065

  • Newcastle Mater Misericordiae Hospital

    Waratah, New South Wales, 2298

  • Queen Elizabeth Hospital

    Woodville, South Australia, 5011

Other trials in Australia

Belgium7 sites

  • Institut Jules Bordet

    Brussels, 1000

  • Hopital Universitaire Erasme

    Brussels, 1070

  • Academisch Ziekenhuis der Vrije Universiteit Brussel

    Brussels, 1090

  • Universitair Ziekenhuis Gent

    Ghent, B-9000

  • Hopital de Jolimont

    Haine-Saint-Paul, 7100

  • Cazk Groeninghe - Campus St-Niklaas

    Kortrijk, B-8500

  • U.Z. Gasthuisberg

    Leuven, B-3000

Other trials in Belgium

Sweden3 sites

  • Sahlgrenska University Hospital

    Gothenburg (Goteborg), S-413 45

  • Karolinska University Hospital/Huddinge

    Stockholm, S-171 76

  • Uppsala University Hospital

    Uppsala, S-75185

Other trials in Sweden

Austria2 sites

  • Allgemeines Krankenhaus der Stadt Wien

    Vienna, A-1090

  • Kaiser Franz Josef Hospital

    Vienna, A-1100

Other trials in Austria

Italy2 sites

  • Ospedale San Martino/Cliniche Universitarie Convenzionate

    Genoa (Genova), 16132

  • Universita di Padova

    Padova, 35128

Other trials in Italy

Netherlands2 sites

  • Leiden University Medical Center

    Leiden, 2300 CA

  • Academisch Ziekenhuis Maastricht

    Maastricht, 6202 AZ

Other trials in Netherlands

Hong Kong1 site

  • Prince of Wales Hospital

    Shatin, N.T.

Other trials in Hong Kong

New Zealand1 site

  • Christchurch Hospital

    Christchurch, 1

Other trials in New Zealand

Norway1 site

  • Haukeland Hospital - University of Bergen

    Bergen, N-5021

Other trials in Norway

Portugal1 site

  • Instituto Portugues de Oncologia Centro do Porto, SA

    Porto, 4200-072

Other trials in Portugal

About this study

Official title: 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.

Read the 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.

Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, liver metastases
Medical subject headings
Colorectal Neoplasms, Neoplasm Metastasis, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startSep 2000

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
IDs, dates and publications
ClinicalTrials.gov ID
NCT00006479
Sponsor's protocol ID
CDR0000068309
Other IDs
EORTC-40983, AGITG-EORTC-40983, ALM-CAO-EORTC-40983, CRUK-LON-EORTC-40983, FFCD-EORTC-40983, EU-20048, CRC-EORTC-40983
Status last verified
Dec 2000
First submitted
6 Nov 2000
Last updated
18 Apr 2011
Results posted
No

Publications

  • 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.

  • 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.

  • 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.

    PubMed 19554377

  • 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.

    PubMed 18358928

  • 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.

  • 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.

    PubMed 26342674

  • 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.

    PubMed 24120480

  • 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.

    PubMed 22314329

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing FOLFOX regimen, fluorouracil and leucovorin calcium in people with Colorectal Cancer and Metastatic Cancer, run by European Organisation for Research and Treatment of Cancer - EORTC at 111 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 18 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 111 sites in France, United Kingdom, Germany, Australia, Belgium and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00006479, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2011.

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