Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic or Recurrent Colorectal Cancer

NCT ID: NCT00416494

Last Updated: 2014-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2014-08-31

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. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving capecitabine and oxaliplatin together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with bevacizumab works in treating patients with metastatic or recurrent colorectal cancer.

Detailed Description

OBJECTIVES:

Primary

• Evaluate the response rate in patients with previously untreated metastatic colorectal cancer treated with capecitabine, oxaliplatin, and bevacizumab.

Secondary

• Assess time to progression (TTP), disease-free survival (DFS), and overall survival (OS) in patients treated with this regimen.
• Assess the safety and tolerability of bevacizumab, oxaliplatin, and capecitabine in patients with previously untreated metastatic colorectal cancer.

Exploratory

• Evaluate the effect of this regimen on the biomarkers of angiogenesis.
• Assess the effect of this regimen on wound angiogenesis.

OUTLINE: Patients receive oral capecitabine twice daily on days 1-5 and 8-12, oxaliplatin IV over 2 hours on day 1, and bevacizumab IV over 1-1½ hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 50 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

Initial Cohort

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

10 mg/kg intravenously over 30-90 minutes on day 1

oxaliplatin

Intervention Type: DRUG

85 mg/m2 intravenously over 2 hours on day 1.

Capecitabine

Intervention Type: DRUG

Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort

Second cohort

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: BIOLOGICAL

10 mg/kg intravenously over 30-90 minutes on day 1

oxaliplatin

Intervention Type: DRUG

85 mg/m2 intravenously over 2 hours on day 1.

Capecitabine

Intervention Type: DRUG

Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort

Interventions

bevacizumab

10 mg/kg intravenously over 30-90 minutes on day 1

Intervention Type: BIOLOGICAL

oxaliplatin

85 mg/m2 intravenously over 2 hours on day 1.

Intervention Type: DRUG

Capecitabine

Oral administration every 12 hours on days 1-5 and 8-12 1000 mg/m2 in initial cohort

Intervention Type: DRUG

Capecitabine

Oral administration every 12 hours on days 1-5 and 8-12 850 mg/m2 in second cohort

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during study and for at least 3-4 months after study completion
• No arterial or venous thrombosis (including cerebrovascular accident) within the last 3 months
• No known, existing, uncontrolled coagulopathy
• No clinically significant cardiac disease
• No congestive heart failure
• No symptomatic coronary artery disease
• No cardiac arrhythmias not well controlled with medication
• No myocardial infarction within the last 12 months
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or bevacizumab
• No history of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the patient at high risk from treatment complications

PRIOR CONCURRENT THERAPY:

• At least 4 weeks since prior sorivudine or brivudine
• At least 6 months since prior adjuvant treatment with fluorouracil and leucovorin calcium or a fluorouracil and leucovorin calcium-based regimen
• No major surgery within 4 weeks without complete recovery
• No prior chemotherapy for metastatic/recurrent disease
• No cancer immunotherapy or other biologic therapy while on therapy
• No radiotherapy while on study
• No hormonal therapy for cancer while on study
• No full-dose warfarin (INR of > 1.5), heparin (> 10,000 units/day), or thrombolytic agents
• Allopurinol and cimetidine should be discontinued prior to starting on this regimen

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Herbert Hurwitz, MD

OTHER

Sponsor Role: lead

Responsible Party

Herbert Hurwitz, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Herbert I. Hurwitz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

References

Hurwitz H, Fernando N, Yu D, et al.: A phase II study of oxaliplatin, capecitabine and bevacizumab in the treatment of metastatic colorectal cancer. [Abstract] Ann Oncol 16 (Suppl 2): A-55P, ii285, 2005.

Reference Type: RESULT

Liu Y, Starr MD, Bulusu A, Pang H, Wong NS, Honeycutt W, Amara A, Hurwitz HI, Nixon AB. Correlation of angiogenic biomarker signatures with clinical outcomes in metastatic colorectal cancer patients receiving capecitabine, oxaliplatin, and bevacizumab. Cancer Med. 2013 Apr;2(2):234-42. doi: 10.1002/cam4.71. Epub 2013 Mar 6.

Reference Type: DERIVED

PMID: 23634291 (View on PubMed)

Other Identifiers

DUMC-4951-05-7R2

Identifier Type: -

Identifier Source: secondary_id

GENENTECH-DUMC-4951-05-7R2

Identifier Type: -

Identifier Source: secondary_id

SANOFI-DUMC-4951-05-7R2

Identifier Type: -

Identifier Source: secondary_id

ROCHE-DUMC-4951-05-7R2

Identifier Type: -

Identifier Source: secondary_id

CDR0000449971

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00008646

Identifier Type: -

Identifier Source: org_study_id