Hepatic Arterial Infusion Plus Chemotherapy in Treating Patients With Colorectal Cancer Metastatic to the Liver

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of hepatic arterial infusion plus chemotherapy in treating patients who have colorectal cancer metastatic to the liver. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different combinations and different ways may kill more tumor cells.

Detailed Description
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OBJECTIVES: I. Determine the safety and toxicity of hepatic arterial infusion with floxuridine and dexamethasone followed by systemic therapy with oxaliplatin and capecitabine in patients with surgically resected liver metastases from primary colorectal carcinoma. II. Determine the 2-year survival rate of patients treated with this regimen. III. Determine the 2-year recurrence rate and time to recurrence in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive floxuridine and dexamethasone intra-arterially continuously on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 6 weeks for 4 courses in the absence of disease recurrence or unacceptable toxicity. After completion of the fourth course, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 2 courses in the absence of disease recurrence or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 2.5 years. PROJECTED ACCRUAL: A total of 15-75 patients will be accrued for this study within 9 months-3.25 years.

Official Title
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A Phase II Trial Evaluating Multiple Metastasectomy Combined With Hepatic Artery Infusion Of Floxuridine (FUDR) And Dexamethasone (DXM), Alternating With Systemic Oxaliplatin (OXAL) And Capecitabine (CAPCIT) For Colorectal Carcinoma Metastatic To The Liver

Conditions
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Adenocarcinoma of the Colon, Adenocarcinoma of the Rectum, Liver Metastases, Recurrent Colon Cancer, Recurrent Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer

Intervention / Treatment
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* Drug: floxuridine
* Drug: dexamethasone
* Drug: oxaliplatin
* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed colorectal adenocarcinoma metastatic to the liver No extrahepatic metastases Prior complete surgical resection of hepatic metastases (at least 1 lesion) within the past 21-56 days Negative surgical margins unless surrounding normal liver tissue was ablated during surgery Radiofrequency ablation may be used as adjunct to surgical resection but not as primary treatment No prior operative ultrasound during resection of hepatic metastases Prior complete surgical resection of carcinoma of colon or rectum (must appear completely resectable in case of synchronous lesions) Performance status - ECOG 0-1 Absolute neutrophil count at least 1,200/mm^3 Platelet count at least 100,000/mm^3 Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN No pre-existing chronic hepatic disease (chronic active hepatitis or cirrhosis) Creatinine no greater than ULN Creatinine clearance greater than 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Adequate oral nutrition (at least 1,500 calories/day) Able to withstand major operative procedure No dehydration No severe anorexia No frequent nausea or vomiting No prior or concurrent malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of any organ No prior or concurrent malignancy associated with more than 10% probability of death from malignant disease within 5 years of diagnosis No concurrent immunotherapy No concurrent colony-stimulating factors during the first course of study therapy No more than 1 prior adjuvant systemic fluorouracil (5-FU) regimen with or without levamisole, leucovorin calcium, or irinotecan One prior 5-FU-based regimen as neoadjuvant treatment for rectal cancer is allowed No prior hepatic artery infusion therapy with 5-FU or floxuridine No prior systemic chemotherapy for metastatic disease No other concurrent chemotherapy No concurrent radiotherapy See Disease Characteristics No prior or concurrent sorivudine or brivudine
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy)<br>Patients receive floxuridine and dexamethasone intra-arterially continuously on days 1-14, oxaliplatin IV over 2 hours on day 22, and oral capecitabine twice daily on days 22-35. Treatment repeats every 6 weeks for 4 courses in the absence of disease recurrence or unacceptable toxicity. After completion of the fourth course, patients receive oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 2 courses in the absence of disease recurrence or unacceptable toxicity. | Drug: floxuridine<br>* Given intra-arterially<br>* Other names: 5-FUDR;Drug: dexamethasone<br>* Given intra-arterially<br>* Other names: DXM;Drug: oxaliplatin<br>* Given IV<br>* Other names: L-OHP;Drug: capecitabine<br>* Given orally<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of oxaliplatin as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC) version 2.0 |  | Up to 6 months | 
| Survival rate |  | From the date of resection, cryoablation, or radiofrequency ablation to up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time | The distribution of survival time will be estimated using the method of Kaplan-Meier. | Time from metastasectomy, cryoablation, or radiofrequency ablation to death due to any cause, assessed up to 3.5 years | 
| Time to recurrence | The distribution of the disease free interval will be estimated using the method of Kaplan-Meier. | Time from metastasectomy, cryoablation, or radiofrequency ablation to documentation of disease recurrence, assessed up to 2 years | 
| Time to treatment failure |  | From the date of metastasectomy, cryoablation, radiofrequency ablation to the date at which the patient is removed from treatment due to recurrence, toxicity, or refusal, assessed up to 3.5 years | 
| Adverse events as assessed by NCI CTC version 2.0 | Patterns of treatment failure, toxicity, including complications associated with the intra-arterial catheter, will be summarized in tabular form. | Up to 3.5 years |