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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: irinotecan hydrochloride; Drug: floxuridine

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 Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: irinotecan hydrochloride; Drug: floxuridine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
time to hepatic recurrence or progression	Up to 2 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Yuman Fong, MD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2003
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: July 8, 2003
• First Submitted That Met QC Criteria: July 8, 2003
• First Posted (Estimate): July 9, 2003

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Irinotecan; Floxuridine
• Other Study ID Numbers: ACOSOG-Z05032; CDR0000305857 (Registry Identifier: NCI Physician Data Query)