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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00006479




Registration number
NCT00006479
Ethics application status
Date submitted
6/11/2000
Date registered
27/01/2003
Date last updated
18/04/2011

Titles & IDs
Public title
Surgery With or Without Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer
Scientific title
Pre- and Post-Operative Chemotherapy With Oxaliplatin 5FU/LV Versus Surgery Alone in Resectable Liver Metastases From Colorectal Origin - Phase III Study
Secondary ID [1] 0 0
EORTC-40983
Secondary ID [2] 0 0
CDR0000068309
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Metastatic Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2000
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Bankstown - Lidcombe Hospital - Bankstown
Recruitment hospital [2] 0 0
Institute of Oncology at Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [4] 0 0
Newcastle Mater Misericordiae Hospital - Waratah
Recruitment hospital [5] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [7] 0 0
Ashford Cancer Centre - Ashford
Recruitment hospital [8] 0 0
Flinder Medical Centres - Bedford Park
Recruitment hospital [9] 0 0
Queen Elizabeth Hospital - Woodville
Recruitment hospital [10] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [11] 0 0
Frankston Hospital - Frankston
Recruitment hospital [12] 0 0
Austin and Repatriation Medical Centre - Heidelberg West
Recruitment hospital [13] 0 0
Mount Hospital - Perth
Recruitment hospital [14] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [15] 0 0
Sir Charles Gairdner Hospital - Perth - Perth
Recruitment postcode(s) [1] 0 0
NSW 2200 - Bankstown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment postcode(s) [5] 0 0
4029 - Brisbane
Recruitment postcode(s) [6] 0 0
4102 - Brisbane
Recruitment postcode(s) [7] 0 0
5035 - Ashford
Recruitment postcode(s) [8] 0 0
5042 - Bedford Park
Recruitment postcode(s) [9] 0 0
5011 - Woodville
Recruitment postcode(s) [10] 0 0
7250 - Launceston
Recruitment postcode(s) [11] 0 0
3199 - Frankston
Recruitment postcode(s) [12] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [13] 0 0
6000 - Perth
Recruitment postcode(s) [14] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Vienna
Country [2] 0 0
Belgium
State/province [2] 0 0
Brussels
Country [3] 0 0
Belgium
State/province [3] 0 0
Ghent
Country [4] 0 0
Belgium
State/province [4] 0 0
Haine Saint Paul
Country [5] 0 0
Belgium
State/province [5] 0 0
Kortrijk
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
France
State/province [7] 0 0
Abbeville
Country [8] 0 0
France
State/province [8] 0 0
Angers
Country [9] 0 0
France
State/province [9] 0 0
Beauvais
Country [10] 0 0
France
State/province [10] 0 0
Besancon
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Boulogne Billancourt
Country [13] 0 0
France
State/province [13] 0 0
Bourg En Bresse
Country [14] 0 0
France
State/province [14] 0 0
Briis Sous Forges
Country [15] 0 0
France
State/province [15] 0 0
Caen
Country [16] 0 0
France
State/province [16] 0 0
Colmar
Country [17] 0 0
France
State/province [17] 0 0
Creteil
Country [18] 0 0
France
State/province [18] 0 0
Dijon
Country [19] 0 0
France
State/province [19] 0 0
Grenoble
Country [20] 0 0
France
State/province [20] 0 0
La Roche Sur Yon
Country [21] 0 0
France
State/province [21] 0 0
Le Mans
Country [22] 0 0
France
State/province [22] 0 0
Libourne
Country [23] 0 0
France
State/province [23] 0 0
Limoges
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
France
State/province [25] 0 0
Montpellier
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Pau
Country [28] 0 0
France
State/province [28] 0 0
Pessac
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Rouen
Country [31] 0 0
France
State/province [31] 0 0
Strasbourg
Country [32] 0 0
France
State/province [32] 0 0
Toulouse
Country [33] 0 0
France
State/province [33] 0 0
Tours
Country [34] 0 0
France
State/province [34] 0 0
Vandoeuvre-les-Nancy
Country [35] 0 0
France
State/province [35] 0 0
Villejuif
Country [36] 0 0
Germany
State/province [36] 0 0
Berlin
Country [37] 0 0
Germany
State/province [37] 0 0
Bochum-Langendreer
Country [38] 0 0
Germany
State/province [38] 0 0
Dessau
Country [39] 0 0
Germany
State/province [39] 0 0
Dresden
Country [40] 0 0
Germany
State/province [40] 0 0
Erlangen
Country [41] 0 0
Germany
State/province [41] 0 0
Essen
Country [42] 0 0
Germany
State/province [42] 0 0
Frankfurt
Country [43] 0 0
Germany
State/province [43] 0 0
Freiburg
Country [44] 0 0
Germany
State/province [44] 0 0
Giessen
Country [45] 0 0
Germany
State/province [45] 0 0
Jena
Country [46] 0 0
Germany
State/province [46] 0 0
Leipzig
Country [47] 0 0
Germany
State/province [47] 0 0
Magdeburg
Country [48] 0 0
Germany
State/province [48] 0 0
Mainz
Country [49] 0 0
Germany
State/province [49] 0 0
Munich
Country [50] 0 0
Germany
State/province [50] 0 0
Regensburg
Country [51] 0 0
Germany
State/province [51] 0 0
Saarbrucken
Country [52] 0 0
Germany
State/province [52] 0 0
Tuebingen
Country [53] 0 0
Germany
State/province [53] 0 0
Wiesbaden
Country [54] 0 0
Germany
State/province [54] 0 0
Wuerzburg
Country [55] 0 0
Hong Kong
State/province [55] 0 0
Shatin, N.T.
Country [56] 0 0
Italy
State/province [56] 0 0
Genoa (Genova)
Country [57] 0 0
Italy
State/province [57] 0 0
Padova
Country [58] 0 0
Netherlands
State/province [58] 0 0
Leiden
Country [59] 0 0
Netherlands
State/province [59] 0 0
Maastricht
Country [60] 0 0
New Zealand
State/province [60] 0 0
Christchurch
Country [61] 0 0
Norway
State/province [61] 0 0
Bergen
Country [62] 0 0
Portugal
State/province [62] 0 0
Porto
Country [63] 0 0
Sweden
State/province [63] 0 0
Gothenburg (Goteborg)
Country [64] 0 0
Sweden
State/province [64] 0 0
Stockholm
Country [65] 0 0
Sweden
State/province [65] 0 0
Uppsala
Country [66] 0 0
United Kingdom
State/province [66] 0 0
England
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Scotland
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Wales
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Other
Name
European Organisation for Research and Treatment of Cancer - EORTC
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australasian Gastro-Intestinal Trials Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Arbeitsgruppe Lebermetastasen und Tumoren
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Cancer Research UK
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Fondation Francaise de Cancerologie Digestive
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00006479
Trial related presentations / 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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bernard Nordlinger, MD
Address 0 0
Hopital Ambroise Pare
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00006479