Cetuximab and Bevacizumab as First-Line Therapy Followed By Combination Chemotherapy and Bevacizumab With or Without Cetuximab as Second-Line Therapy in Treating Patients With Stage IV 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: NCT00571740
Recruitment Status : Withdrawn (The study was not activated)
First Posted : December 12, 2007
Last Update Posted : July 6, 2016
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

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 oxaliplatin, leucovorin, 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 monoclonal antibodies together with combination chemotherapy may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying how well giving cetuximab together bevacizumab works as first-line therapy, followed by combination chemotherapy and bevacizumab with or without cetuximab as second-line therapy in treating patients with stage IV colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Biological: bevacizumab Biological: cetuximab Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Phase II Trial of Cetuximab/Bevacizumab (CB) as Palliative First-Line Therapy in Patients With Advanced Colorectal Cancer Followed by FOLFOX+CB vs. FOLFOX+B

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Arm I (second-line therapy)
Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: Arm II (second-line therapy)
Patients receive bevacizumab and modified FOLFOX7 as in arm I. Patients also receive cetuximab IV over 2 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Biological: cetuximab
Given IV
Drug: fluorouracil
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV

Primary Outcome Measures :
  1. Progression-free survival (PFS) rate at 6 months [ Time Frame: at 6 months ]

Secondary Outcome Measures :
  1. Tumor response rate associated with second-line therapy [ Time Frame: up to 3 years ]
  2. Time to progression during second-line therapy [ Time Frame: up to 3 years ]
  3. Duration of response [ Time Frame: up to 3 years ]
  4. Quality of life [ Time Frame: up to 3 years ]

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


  • Histologically confirmed stage IV colorectal cancer
  • Measurable disease, defined as at least one lesion whose longest diameter can be accurately measured as ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
  • Must not be a candidate for neoadjuvant therapy
  • No CNS or brain metastases


  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 3 times ULN
  • AST ≤ 3 times ULN
  • Creatinine ≤ 1.5 x times ULN
  • Proteinuria < 1+ by urinalysis OR proteinuria < 1 g by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • English-speaking patients must have the ability to complete questionnaires by themselves or with assistance
  • Must be willing to provide blood and tissue samples for research purposes
  • No history of hypertensive crisis or hypertensive encephalopathy
  • No blood pressure > 150/100 mm Hg
  • No New York Heart Association (NYHA) class II-IV congestive heart failure
  • No myocardial infarction or unstable angina within the past 6 months
  • No stroke or transient ischemic attack within the past 6 months
  • No clinically significant vascular disease (e.g., aortic aneurysm or aortic dissection)
  • No clinically significant peripheral vascular disease
  • No evidence of bleeding diathesis or coagulopathy
  • No significant traumatic injury within the past 28 days
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
  • No serious nonhealing wound, ulcer, or bone fracture


  • No prior nonsurgical treatment for stage IV disease

    • Adjuvant therapy allowed if completed > 6 months prior to study registration
  • More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study
  • No prior therapy that specifically and directly targets the EGFR pathway
  • No prior monoclonal antibody therapy
  • More than 28 days since prior major surgery or open biopsy
  • More than 7 days since prior minor surgery, such as fine-needle aspirations or core biopsies

    • Placement of a vascular access device does not have to meet this criterion
  • No concurrent major surgery

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): NCT00571740

Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Study Chair: Axel Grothey, MD Mayo Clinic

Responsible Party: Alliance for Clinical Trials in Oncology Identifier: NCT00571740     History of Changes
Other Study ID Numbers: N0548
CDR0000578111 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2009-00651 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
First Posted: December 12, 2007    Key Record Dates
Last Update Posted: July 6, 2016
Last Verified: July 2016

Keywords provided by Alliance for Clinical Trials in Oncology:
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
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
Protective Agents