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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Herbert Hurwitz, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00290615
First received: February 9, 2006
Last updated: March 25, 2013
Last verified: March 2013
  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
Biological: bevacizumab
Biological: cetuximab
Drug: capecitabine
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Oxaliplatin, Capecitabine, Cetuximab, and Bevacizumab in the Treatment of Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Duke University:

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

    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



Secondary Outcome Measures:
  • Safety and Tolerability [ Time Frame: After all participants went off study drug regimine. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]
    Average months of survival of participants after receiving study drug.


Other Outcome Measures:
  • Effect on Angiogenesis Biomarkers [ Time Frame: After study completion ] [ Designated as safety issue: No ]
  • Effect on Wound Angiogenesis [ Time Frame: After study completion ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: January 2006
Study Completion Date: January 2011
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: bevacizumab
Other Name: Avastin
Biological: cetuximab Drug: capecitabine Drug: oxaliplatin

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.

  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
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 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
Herbert Hurwitz
Investigators
Study Chair: Herbert I. Hurwitz, MD Duke Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Herbert Hurwitz, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00290615     History of Changes
Other Study ID Numbers: Pro00007431 (CDR0000449945), DUMC-7118-05-4R0
Study First Received: February 9, 2006
Results First Received: February 12, 2013
Last Updated: March 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Cetuximab
Capecitabine
Oxaliplatin
Fluorouracil
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 16, 2014