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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00006479
Recruitment Status : Unknown
Verified December 2000 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : January 27, 2003
Last Update Posted : April 18, 2011
Sponsor:
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)

Study Description
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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.


Condition or disease Intervention/treatment 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 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Primary Purpose: 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
Study Start Date : September 2000
Arms and Interventions
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Outcome Measures
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Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006479


Locations
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Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Australasian Gastro-Intestinal Trials Group
Arbeitsgruppe Lebermetastasen und Tumoren
Cancer Research UK
Fondation Francaise de Cancerologie Digestive
Investigators
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OverallOfficial: 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 University Hospital Southampton NHS Foundation Trust
Study Chair: Philippe Rougier, MD Hopital Ambroise Pare
More Information
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Publications of Results:
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.
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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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ClinicalTrials.gov Identifier: NCT00006479    
Other 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
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: April 18, 2011
Last Verified: December 2000
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:
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Colorectal Neoplasms
Neoplasm Metastasis
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
Leucovorin
 Fluorouracil
Oxaliplatin
Calcium
Levoleucovorin
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex