Hepatic Arterial Infusion With Floxuridine and Systemic Irinotecan After Surgery in Treating Patients With Hepatic (Liver) Metastases From Colorectal Cancer

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00063960

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

9.4

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy such as floxuridine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery.

PURPOSE: Phase II trial to study the effectiveness of systemic irinotecan and hepatic arterial infusion with floxuridine after surgery in treating patients who have hepatic (liver) metastases from colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Drug: floxuridine Drug: irinotecan hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Determine the toxicity of hepatic arterial infusion with floxuridine and systemic irinotecan adjuvant to liver metastases resection or ablation with or without resection in patients with hepatic metastases secondary to colorectal cancer.
Determine the overall survival of patients treated with this regimen.
Determine the time to any hepatic recurrence or progression in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to prior therapy (liver metastases resection only vs ablation with or without resection).

Within 4-8 weeks after prior resection or ablation, patients receive hepatic arterial infusion of floxuridine continuously on days 1-14 and irinotecan IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity.

Patients are followed every 3 months for 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

94 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial Of Toxicity Assessment In Two Cohorts Of Patients (Resection Alone Or Ablation With Or Without Resection Of Hepatic Metastases From Colorectal Cancer) Treated With Adjuvant Hepatic Arterial Infusion (HAI) FUDR Plus Systemic CPT-11

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

Dec 1, 2004

Actual Study Completion Date :

Dec 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: floxuridine + irinotecan Within 4-8 weeks after prior resection or ablation, patients receive hepatic arterial infusion of floxuridine continuously on days 1-14 and irinotecan IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of unacceptable toxicity. Patients are followed every 3 months for 2 years.	Drug: floxuridine Drug: irinotecan hydrochloride

Arm

Intervention/Treatment

Experimental: floxuridine + irinotecan

Drug: floxuridine

Drug: irinotecan hydrochloride

Outcome Measures

Primary Outcome Measures

overall survival [Up to 2 years]

Secondary Outcome Measures

time to hepatic recurrence or progression [Up to 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed metastatic colorectal adenocarcinoma
Primary colorectal adenocarcinoma that has been completely resected (R0 disease)
No evidence of residual, viable tumor by abdominal/pelvic helical CT scan or MRI with IV contrast
Metastatic disease
No more than 9 liver metastases
All lesions completely resected or completely treated by ablation (with or without resection)
All lesions treated by ablation must have been less than 5 cm in size and at least 5 mm away from main/left/right portal vein, common bile duct, and inferior vena cava
All resected lesions must have a negative surgical margin (R0)
Disease progression after prior systemic irinotecan for metastatic disease allowed
No extrahepatic metastases confirmed by chest CT scan except colorectal mesenteric lymph node metastases resected at the time of primary tumor resection
No other prior resection of extrahepatic metastases
Must have the entire liver remnant perfused with a single catheter
Must have a nuclear medicine macro-aggregated albumin flow scan to confirm the area of pump perfusion before study registration

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2 OR
Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

WBC at least 3,000/mm^3
Absolute granulocyte count at least 1,500/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 2 mg/dL
Alkaline phosphatase no greater than 2.0 times upper limit of normal (ULN)
AST and ALT no greater than 2.0 times ULN
No active hepatitis B or C infection
No histological evidence of cirrhosis

Renal

Creatinine no greater than 1.5 times ULN
Calcium less than 1.3 times ULN

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Postmenopausal women must be amenorrheic for at least 12 consecutive months to be deemed not fertile
Medically fit to begin chemotherapy between 4 and 8 weeks after surgery
Prior cancer allowed if all of the following criteria are met:
Undergone potentially curative therapy for all prior malignancies
No other malignancy within the past 5 years except the following:
Effectively treated basal cell or squamous cell skin cancer
Carcinoma in situ of the cervix that has been effectively treated by surgery alone
Lobular carcinoma in situ of the ipsilateral or contralateral breast treated by surgery alone
No evidence of recurrence of any prior malignancy
No prior hepatic arterial infusion pump malfunction, malperfusion, or infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent immunologic or biologic therapy

Chemotherapy

No prior chemotherapy within 4 weeks before hepatic resection or hepatic ablation (with or without resection)
No prior hepatic arterial infusion with fluorouracil or floxuridine

Radiotherapy

No concurrent adjuvant radiotherapy to the pelvis
No other concurrent radiotherapy

Other

No other concurrent systemic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	Central Baptist Hospital	Lexington	Kentucky	United States	40503-9985
3	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
4	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
5	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
6	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
7	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7213
8	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
9	Integris Oncology Services	Oklahoma City	Oklahoma	United States	73112
10	University Medical Group	Providence	Rhode Island	United States	02908-4735