Cetuximab, Leucovorin, Oxaliplatin, and Fluorouracil With or Without Bevacizumab in Treating Patients With Resectable 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. Identifier: NCT00438737
Recruitment Status : Unknown
Verified September 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : February 22, 2007
Last Update Posted : September 2, 2011
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Monoclonal antibodies, such as cetuximab and bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor.Drugs used in chemotherapy, such as leucovorin, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy and bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving these treatments after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This randomized phase II trial is studying the side effects and how well giving cetuximab together with leucovorin, oxaliplatin, and fluorouracil works with or without bevacizumab in treating patients with resectable liver metastases from colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Cancer Biological: bevacizumab Biological: cetuximab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Phase 2

Detailed Description:


  • Compare the safety and activity of neoadjuvant and adjuvant cetuximab, leucovorin calcium, oxaliplatin, and fluorouracil with vs without bevacizumab in patients with resectable liver metastases secondary to colorectal cancer.

OUTLINE: This is an open-label, randomized, multicenter study. Patient are stratified according to participating center and planned liver resection (major [≥ 3 segments] vs minor [< 3 segments]). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive leucovorin calcium IV over 2 hours and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV over 46 hours (FOLFOX) beginning on day 1. Patients also receive cetuximab IV over 1-2 hours on days 1 and 8. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Between 3-5 weeks after completion of FOLFOX and cetuximab, patients undergo liver resection. Beginning between 4-8 weeks after surgery, patients receive another 6 courses of FOLFOX and cetuximab as in neoadjuvant therapy.

  • Arm II: Patients receive FOLFOX and cetuximab as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 14 days for 6 courses* in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients do not receive bevacizumab during course 6

Between 3-5 weeks after completion of FOLFOX, cetuximab, and bevacizumab, patients undergo liver resection. Beginning between 4-8 weeks after surgery, patients receive another 6 courses of FOLFOX, cetuximab, and bevacizumab as in neoadjuvant therapy.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for at least 3 years.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial Evaluating the Feasibility and Tolerance of the Combination of FOLFOX With Cetuximab and the Combination of FOLFOX With Cetuximab and Bevacizumab as Perioperative Treatment in Patients With Resectable Liver Metastases From Colorectal Cancer
Study Start Date : January 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab
U.S. FDA Resources

Primary Outcome Measures :
  1. Response rate (preoperative response rate)
  2. Safety (rate of perioperative safety findings)

Secondary Outcome Measures :
  1. Progression-free survival
  2. Pathological resection rate
  3. Overall survival

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of metastatic colorectal cancer, meeting all of the following criteria:

    • Metachronous or synchronous liver metastases

      • Metastases potentially completely resectable

        • No requirement for resection combined with cryotherapy or radiofrequency ablation
    • Must have undergone complete resection (R0) of the primary tumor within the past 4 weeks
  • Measurable liver metastases
  • No evidence of extrahepatic disease

    • 1 or 2 resectable lung metastases allowed


  • WHO performance status 0-1
  • Absolute neutrophil count > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 9 g/dL
  • WBC > 3,000/mm³
  • Creatinine < 1.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN
  • AST and ALT < 5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant proteinuria (i.e., protein > 500 mg/24-hour urine collection)
  • No known allergy to any of the study drugs (including excipients) or any related compound, including hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • No bleeding diathesis or coagulopathy
  • No peripheral neuropathy > grade 1
  • No serious nonhealing wound, ulcer, or bone fracture
  • No clinically significant cardiovascular disease, including any of the following:

    • Uncontrolled hypertension
    • New York Heart Association class II-IV congestive heart failure
    • Unstable angina pectoris within the past 12 months
    • Peripheral vascular disease ≥ grade 2
    • Serious cardiac arrhythmia requiring medication
    • Myocardial infarction within the past 12 months
    • Cerebrovascular accident or transient ischemic attack within the past 12 months
  • No symptomatic diverticulitis or known gastroduodenal ulceration
  • No significant traumatic injury within the past 4 weeks
  • No known alcohol or drug abuse
  • No psychological, familial, social, or geographical condition that would preclude study compliance
  • No other significant disease that would preclude study participation


  • See Disease Characteristics
  • No prior chemotherapy for metastatic disease
  • At least 1 month since prior major surgical procedure or open biopsy
  • More than 30 days since prior participation in another clinical study
  • Prior adjuvant chemotherapy for primary cancer allowed provided the following criteria are met:

    • At least 12 months since prior oxaliplatin-containing adjuvant therapy
    • No persistent neuropathy
  • No prior therapy targeting the epidermal growth factor receptor or vascular endothelial growth factor (VEGF)/VEGF receptor
  • No concurrent regular use of acetylsalicylic acid (> 325 mg/day) or other nonsteroidal anti-inflammatory drugs
  • No concurrent full-dose anticoagulation
  • No concurrent prophylactic hematopoietic growth factors
  • No concurrent allopurinol

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 identifier (NCT number): NCT00438737

Hopital Ambroise Pare
Boulogne, France, F-92104
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
OverallOfficial: Bernard Nordlinger, MD Hopital Ambroise Pare Identifier: NCT00438737     History of Changes
Other Study ID Numbers: CDR0000530116
First Posted: February 22, 2007    Key Record Dates
Last Update Posted: September 2, 2011
Last Verified: September 2007

Keywords provided by National Cancer Institute (NCI):
liver metastases
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors