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Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Duke University
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00290615
  Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. Cetuximab and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine together with cetuximab, oxaliplatin, and bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving capecitabine together with cetuximab, oxaliplatin, and bevacizumab works in treating patients with metastatic or recurrent colorectal cancer that cannot be removed by surgery.


Condition Intervention Phase
Colorectal Cancer
Drug: bevacizumab
Drug: capecitabine
Drug: cetuximab
Drug: oxaliplatin
Phase II

MedlinePlus related topics: Cancer Colorectal Cancer
Drug Information available for: Capecitabine Bevacizumab Oxaliplatin Cetuximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Study of Oxaliplatin, Capecitabine, Cetuximab, and Bevacizumab in the Treatment of Metastatic Colorectal Cancer

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

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability [ Designated as safety issue: Yes ]
  • Progression-free and overall survival [ Designated as safety issue: No ]
  • Effect on angiogenesis biomarkers [ Designated as safety issue: No ]
  • Effect on wound angiogenesis [ Designated as safety issue: No ]

Estimated Enrollment: 45
Study Start Date: January 2006
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate in patients with unresectable metastatic or recurrent colorectal adenocarcinoma treated with capecitabine, cetuximab, oxaliplatin, and bevacizumab.

Secondary

  • Determine the safety and tolerability of this regimen in these patients.
  • Determine the progression-free and overall survival of patients treated with this regimen.
  • Determine the effect of this regimen on the angiogenesis biomarkers in these patients.
  • Determine the effect of this regimen on wound angiogenesis in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral capecitabine twice daily on days 1-14. Patients will also receive cetuximab IV over 1-2 hours, oxaliplatin IV over 2 hours, and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 1 month.

PROJECTED ACCRUAL: Approximately 45 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the colon or rectum

    • Unresectable disease
    • Metastatic or recurrent disease
  • Not amenable to potentially curative treatment
  • No untreated leptomeningeal or brain metastases

PATIENT CHARACTERISTICS:

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 2,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • No known uncontrolled coagulopathy

Hepatic

  • AST and ALT < 2.5 times upper limits of normal (ULN) (5 times ULN if liver metastases are present)
  • Bilirubin < 2.0 times ULN

Renal

  • Creatinine clearance > 40 mL/min
  • Urine protein negative
  • Urine protein:creatinine ratio > 1

Cardiovascular

  • No unstable or uncontrolled hypertension (i.e., blood pressure [BP] > 150/100 mm Hg despite antihypertensive therapy)

    • Patients who recently started or have adjusted antihypertensive medications are eligible provided BP is < 140/90 mm Hg for ≥ 3 different measurements over 14 days
  • No arterial thromboembolic events within the past 6 months, including any of the following:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina
    • Myocardial infarction
    • Clinically significant peripheral vascular disease
  • No New York Heart Association class III-IV congestive heart failure
  • No uncontrolled symptomatic coronary artery disease or cardiac arrhythmia
  • No other significant uncontrolled cardiac disease

Gastrointestinal

  • No lack of physical integrity of the upper gastrointestinal tract
  • No malabsorption syndrome
  • No inability to tolerate oral medication

Immunologic

  • No prior severe infusion reaction to a monoclonal antibody
  • No history of an allergic reaction attributed to compounds of similar chemical or biologic composition to oxaliplatin, cetuximab, capecitabine, or bevacizumab
  • No prior unanticipated, severe reaction to fluoropyrimidine therapy or known hypersensitivity to fluoroucacil

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during the study and for 3-4 months after completion of study treatment
  • No peripheral neuropathy ≥ grade 2
  • No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No known dihydropyrimidine dehydrogenase deficiency

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior adjuvant bevacizumab or cetuximab
  • No other concurrent anticancer immunotherapy or biologic therapy

Chemotherapy

  • At least 6 months since a prior adjuvant fluorouracil-, leucovorin calcium-, or capecitabine-based regimen
  • At least 12 months since prior adjuvant oxaliplatin
  • No prior chemotherapy for metastatic or recurrent disease

Endocrine therapy

  • No concurrent hormonal therapy

Radiotherapy

  • No concurrent radiotherapy

Surgery

  • More than 4 weeks since prior major surgery and recovered
  • More than 6 months since vascular surgery, stenting, or angioplasty

Other

  • At least 4 weeks since prior and no concurrent sorivudine or brivudine
  • More than 4 weeks since prior participation in any investigational drug study
  • No prior therapy that affects or targets the epidermal growth factor pathway
  • No concurrent cimetidine

    • Concurrent ranitidine, famotidine, or proton-pump inhibitors allowed
  • Concurrent anticoagulation therapy with full-dose anticoagulant allowed provided dose is stable for at least 2 weeks
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290615

Locations
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
Sponsors and Collaborators
Duke University
Investigators
Study Chair: Herbert I. Hurwitz, MD Duke University
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Responsible Party: Duke Comprehensive Cancer Center ( Herbert I. Hurwitz )
Study ID Numbers: CDR0000449945, DUMC-7118-05-4R0
Study First Received: February 9, 2006
Last Updated: December 13, 2008
ClinicalTrials.gov Identifier: NCT00290615  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer

Study placed in the following topic categories:
Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases
Bevacizumab
Intestinal Diseases
Rectal Diseases
Recurrence
Intestinal Neoplasms
Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009