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Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery

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ClinicalTrials.gov Identifier: NCT00290615
Recruitment Status : Completed
First Posted : February 13, 2006
Results First Posted : May 7, 2013
Last Update Posted : May 7, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Herbert Hurwitz, Duke University

Tracking Information
First Submitted Date  ICMJE February 9, 2006
First Posted Date  ICMJE February 13, 2006
Results First Submitted Date  ICMJE February 12, 2013
Results First Posted Date  ICMJE May 7, 2013
Last Update Posted Date May 7, 2013
Study Start Date  ICMJE January 2006
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 25, 2013)
Response Rate (Percentage of Participants With Partial or Complete Response) [ Time Frame: After all subjects were evaluated for restaging which occured every 9 weeks from drug initiation until disease progression, assesed up to 24 months. ]
Restaging scans occurred every 9 weeks from time of study drug initiation until disease progression. Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. The definitions were: Complete response (CR)- Disappearance of all target lesions Partial response (PD)- At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Stable disease (SD)- Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00290615 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2013)
  • Safety and Tolerability [ Time Frame: After all participants went off study drug regimine. ]
    Number of participants with adverse events
  • Progression-free Survival [ Time Frame: From time of treatment until documented progression or death from any cause, whichever came first, assesed up to 60 months. ]
    Disease assessment was performed and recorded according to the Response Evaluation Criteria in Solid Tumors (RECIST v.1.0) Guidelines. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. This is the average number of months participants survived without showing progressive disease.
  • Overall Survival [ Time Frame: From time of treatment until death from any cause, assesed up to 60 months. ]
    Average months of survival of participants after receiving study drug.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: March 25, 2013)
  • Effect on Angiogenesis Biomarkers [ Time Frame: After study completion ]
  • Effect on Wound Angiogenesis [ Time Frame: After study completion ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Capecitabine, Cetuximab, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer That Cannot Be Removed By Surgery
Official Title  ICMJE Phase II Study of Oxaliplatin, Capecitabine, Cetuximab, and Bevacizumab in the Treatment of Metastatic Colorectal Cancer
Brief Summary

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.

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.

Exploratory

  • 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: bevacizumab
    Other Name: Avastin
  • Biological: cetuximab
  • Drug: capecitabine
  • Drug: oxaliplatin
Study Arms  ICMJE Experimental: Capecitabine, Oxaliplatin, Bevacizumab, Cetuximab

Capecitabine - oral administration of 850 mg/m2 every 12 hours on days 1-14. Oxaliplatin - IV administration of 130 mg/m2 over 2 hours on day 1 of a cycle. Bevacizumab- IV administration of 7.5 mg/kg over 30-90 minutes on day 1 of a cycle.

Cetuximab at an initial dose of 400 mg/m2 over 120 minutes and subsequently 250 mg/m2 over 60 minutes on day 1 of a cycle.

Cycles are 21 days.

Interventions:
  • Biological: bevacizumab
  • Biological: cetuximab
  • Drug: capecitabine
  • Drug: oxaliplatin
Publications * Wong NS, Fernando NH, Nixon AB, Cushman S, Aklilu M, Bendell JC, Morse MA, Blobe GC, Ashton J, Pang H, Hurwitz HI. A phase II study of capecitabine, oxaliplatin, bevacizumab and cetuximab in the treatment of metastatic colorectal cancer. Anticancer Res. 2011 Jan;31(1):255-61.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2013)
30
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2011
Actual Primary Completion Date January 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00290615
Other Study ID Numbers  ICMJE Pro00007431 (CDR0000449945)
DUMC-7118-05-4R0
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Herbert Hurwitz, Duke University
Study Sponsor  ICMJE Herbert Hurwitz
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Herbert I. Hurwitz, MD Duke Cancer Institute
PRS Account Duke University
Verification Date March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP