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Cetuximab, Leucovorin, Oxaliplatin, and Fluorouracil With or Without Bevacizumab in Treating Patients With Resectable Liver Metastases From Colorectal Cancer

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: February 20, 2007
Last updated: September 1, 2011
Last verified: September 2007

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 Intervention 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

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (preoperative response rate)
  • Safety (rate of perioperative safety findings)

Secondary Outcome Measures:
  • Progression-free survival
  • Pathological resection rate
  • Overall survival

Estimated Enrollment: 100
Study Start Date: January 2007
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.


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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: 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
  More Information Identifier: NCT00438737     History of Changes
Other Study ID Numbers: CDR0000530116
Study First Received: February 20, 2007
Last Updated: September 1, 2011

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 processed this record on August 18, 2017