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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00026234

Collaborator

NSABP Foundation Inc (Other)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Colon Adenocarcinoma of the Rectum Liver Metastases Recurrent Colon Cancer Recurrent Rectal Cancer Stage IV Colon Cancer Stage IV Rectal Cancer	Drug: floxuridine Drug: dexamethasone Drug: oxaliplatin Drug: capecitabine	Phase 2

Detailed Description

OBJECTIVES:

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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Jan 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (chemotherapy) 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 Given intra-arterially Other Names: 5-FUDR Drug: dexamethasone Given intra-arterially Other Names: Aeroseb-Dex Decaderm Decadron DM DXM Drug: oxaliplatin Given IV Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP Drug: capecitabine Given orally Other Names: CAPE Ro 09-1978/000 Xeloda

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy)

Drug: floxuridine

Given intra-arterially

Other Names:

5-FUDR

Drug: dexamethasone

Given intra-arterially

Other Names:

Aeroseb-Dex

Decaderm

Decadron

DXM

Drug: oxaliplatin

Given IV

Other Names:

1-OHP

Dacotin

Dacplat

Eloxatin

L-OHP

Drug: capecitabine

Given orally

Other Names:

CAPE

Ro 09-1978/000

Xeloda

Outcome Measures

Primary Outcome Measures

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

Survival time [Time from metastasectomy, cryoablation, or radiofrequency ablation to death due to any cause, assessed up to 3.5 years]
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time to recurrence [Time from metastasectomy, cryoablation, or radiofrequency ablation to documentation of disease recurrence, assessed up to 2 years]
The distribution of the disease free interval will be estimated using the method of Kaplan-Meier.
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 [Up to 3.5 years]
Patterns of treatment failure, toxicity, including complications associated with the intra-arterial catheter, will be summarized in tabular form.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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