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

NCT ID: NCT00290615

Last Updated: 2013-05-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2011-01-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

cetuximab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

Interventions

bevacizumab

Intervention Type: BIOLOGICAL

cetuximab

Intervention Type: BIOLOGICAL

capecitabine

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Herbert Hurwitz

OTHER

Sponsor Role: lead

Responsible Party

Herbert Hurwitz

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Herbert I. Hurwitz, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21273607 (View on PubMed)

Other Identifiers

DUMC-7118-05-4R0

Identifier Type: -

Identifier Source: secondary_id

Pro00007431 (CDR0000449945)

Identifier Type: -

Identifier Source: org_study_id