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NCT00006479 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
UNKNOWN
Registry last update
2011-04-18

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
80 Years
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
interventions
  1. name
    FOLFOX regimen
    type
    DRUG
  2. name
    fluorouracil
    type
    DRUG
  3. name
    leucovorin calcium
    type
    DRUG
  4. name
    oxaliplatin
    type
    DRUG
  5. name
    adjuvant therapy
    type
    PROCEDURE
  6. name
    conventional surgery
    type
    PROCEDURE
  7. name
    neoadjuvant therapy
    type
    PROCEDURE
Study design
primary Purpose
TREATMENT
EnrollmentSource null
Registered outcome plans (not posted results)
Full study description
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.
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.
Source references
references
  1. citation
    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.
    type
    RESULT
  2. citation
    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.
    type
    RESULT
  3. citation
    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
    type
    RESULT
  4. citation
    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
    type
    RESULT
  5. citation
    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.
    type
    RESULT
  6. citation
    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.
    type
    RESULT
  7. citation
    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.
    type
    RESULT
  8. citation
    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.
    type
    RESULT
  9. citation
    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
    type
    DERIVED
  10. citation
    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
    type
    DERIVED
  11. citation
    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
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        24.7 months for FOLFIRI; HR, 0.89; log-rank <em>P</em> = .44) or OS (HR, 1.09; 95% CI, 0.72&#8211;1.64).</li></ul></div></li><li>The <a href="/clinicaltrials/NCT00006479">EORTC-40983</a> trial (NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery
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        log-rank <em>P</em> = .44) or OS (HR, 1.09; 95% CI, 0.72&#8211;1.64).</li></ul></div></li><li>The <a href="/clinicaltrials/NCT00006479">EORTC-40983</a> trial (NCT00006479) randomly assigned 364 patients with up to four resectable liver metastases to perioperative FOLFOX (six cycles presurgery and six cycles postsurgery) or surge
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      source update dates
      1. context
        Updated: February 12, 2025
        datetime
        2025-02-12T12:00:00Z
        display
        February 12, 2025

    Preserved source evidence · Not medical advice