Oxaliplatin, Capecitabine, and Bevacizumab Followed By Surgery and/or Radiofrequency Ablation in Patients With Colorectal Cancer

Sponsor

University of California, Davis (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00408772

Collaborator

Sanofi (Industry)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, 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 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiofrequency ablation uses a high-frequency, electric current to kill tumor cells. Giving chemotherapy and bevacizumab before surgery or radiofrequency ablation may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with bevacizumab followed by surgery and/or radiofrequency ablation works in treating patients with colorectal cancer that has spread to the liver and cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Biological: bevacizumab Drug: capecitabine Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiofrequency ablation	Phase 2

Detailed Description

OBJECTIVES:

Primary

Evaluate the conversion rate of nonresectable disease to resectable disease in patients with nonresectable liver metastases secondary to colorectal adenocarcinoma treated with neoadjuvant therapy comprising oxaliplatin, capecitabine, and bevacizumab followed by hepatic resection and/or radiofrequency ablation.
Evaluate progression-free survival of patients treated with this regimen.

Secondary

Determine disease-free and overall survival of patients treated with this regimen.
Determine the toxicities of this regimen in these patients.

OUTLINE:

Neoadjuvant therapy: Patients receive oxaliplatin IV over 2 hours and bevacizumab IV over 1 hour on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 4-6 courses in the absence of disease progression or unacceptable toxicity or until conversion to resectable disease.
Surgery and/or radiofrequency ablation (RFA): Patients undergo hepatic resection (with or without RFA) when tumor is deemed resectable. Patients with stable (< 8 lesions) and unresectable disease undergo laparoscopic or percutaneous RFA. RFA repeats once 4-6 weeks later.
Adjuvant therapy: Beginning 6-8 weeks after surgery and/or RFA, patients may receive adjuvant therapy comprising oxaliplatin, capecitabine, and bevacizumab, as in neoadjuvant therapy, for up to 4 courses.

After completion of study treatment, patients are followed every 4 months.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy of Neoadjuvant XELOX/AVASTIN Therapy for Nonresectable Colorectal Liver Metastases With Secondary Hepatic Resection/Radiofrequency

Study Start Date :

Jun 1, 2007

Actual Primary Completion Date :

Apr 1, 2008

Actual Study Completion Date :

Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Unresectable colorectal liver mets	Biological: bevacizumab Drug: capecitabine Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiofrequency ablation

Arm

Intervention/Treatment

Experimental: Unresectable colorectal liver mets

Biological: bevacizumab

Drug: capecitabine

Drug: oxaliplatin

Procedure: conventional surgery

Procedure: neoadjuvant therapy

Procedure: radiofrequency ablation

Outcome Measures

Primary Outcome Measures

Conversion rate of nonresectable disease to resectable disease [48 months]

Secondary Outcome Measures

Disease-free and overall survival [48 months]
Objective response rate [48 months]
Duration of response [48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed colorectal adenocarcinoma metastatic to the liver
Unresectable liver metastases
Measurable disease
No evidence of extrahepatic metastases
No CNS metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Absolute neutrophil count > 1,500/mm^3
Platelet count > 100,000/mm^3
Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 45 mL/min
Urinary protein < 2+ by dipstick OR < 2 g by 24-hour urine collection
Bilirubin < 2 times ULN
SGOT and SGPT < 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 18 months after completion of study therapy
Able to take oral medications (e.g., no dysphagia or malabsorption symptoms)
No other prior malignancy unless in complete remission and off therapy for ≥ 5 years
No known allergy to the study drugs
No peripheral neuropathy > grade 1
No uncontrolled infection
No uncontrolled hypertension
No active bleeding or hemoptysis
No other serious concurrent illness within the past 12 months, including any of the following:
Nonstable coronary artery disease
Myocardial infarction
Transient ischemic attack
Cardiovascular accident

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy
At least 28 days since prior major surgery
Prior therapy for advanced disease allowed
No prior oxaliplatin-based therapy
Concurrent maintenance and palliative treatment during study chemotherapy allowed (e.g., nutritional or transfusional support or pain control)
No concurrent corticosteroids except when used under the following circumstances:
As oxaliplatin premedication
Anti-5-HT_3 as antiemetic
No concurrent cold cap or iced mouth rinses
No other concurrent chemotherapy
No placement of hepatic artery port for regional chemotherapy