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Chemotherapy With or Without Isolated Hepatic Perfusion With Melphalan in Treating Patients With Colorectal Cancer That Has Spread to the Liver

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00020501
First Posted: January 27, 2003
Last Update Posted: March 8, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
National Institutes of Health Clinical Center (CC)
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways may kill more tumor cells. It is not yet known which chemotherapy regimen is most effective for colorectal cancer that has spread to the liver.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without isolated hepatic perfusion with melphalan in treating patients who have colorectal cancer that has spread to the liver.


Condition Intervention Phase
Colorectal Cancer Metastatic Cancer Drug: FOLFIRI regimen Drug: floxuridine Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: melphalan Procedure: hyperthermia treatment Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Prospective Random Assignment Trial of Regional and Systemic Chemotherapy With or Without Initial Isolated Hepatic Perfusion for Patients With Metastatic Unresectable Colorectal Cancers of the Liver

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Study Start Date: March 2001
Study Completion Date: January 2005
Detailed Description:

OBJECTIVES:

  • Compare the disease-free and overall survival of patients with unresectable colorectal cancer metastatic to the liver treated with regional and systemic chemotherapy with or without isolated hepatic perfusion with melphalan.
  • Compare the response rate and duration of response in patients treated with these regimens.
  • Compare the patterns of recurrence (liver vs systemic) in patients treated with these regimens.
  • Compare the health-related quality of life (QOL) of patients treated with these regimens.
  • Determine whether baseline QOL correlates with length of survival of patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for liver metastasis (yes vs no) and percentage of hepatic replacement (less than 25% vs at least 25%). All patients undergo laparotomy to determine final eligibility. Eligible patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo hyperthermic isolated hepatic perfusion with melphalan over 60 minutes. Patients then undergo placement of an intrahepatic pump or port. At 6 weeks post hepatic perfusion, patients receive systemic chemotherapy comprising irinotecan IV over 90 minutes on day 1 followed by fluorouracil IV over 15 minutes and leucovorin calcium (CF) IV over 15 minutes on days 1-3. Patients receive local chemotherapy comprising floxuridine (FUDR) and CF by hepatic arterial infusion (HAI) continuously on days 14-28.
  • Arm II: Patients undergo placement of an intrahepatic pump or port at laparotomy. At 7 days post laparotomy, patients receive FUDR and CF by HAI continuously for 14 days. Beginning 2 weeks after completion of HAI, patients receive systemic and local chemotherapy as in arm I.

Treatment with combined systemic and local chemotherapy repeats every 35 days for a maximum of 6 courses. Treatment with local chemotherapy alone repeats every 28 days for a maximum of 6 additional courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, postoperatively, every third course of chemotherapy, every 3 months for 2 years, and then every 6 months thereafter.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 168 patients (84 per treatment arm) will be accrued for this study within 54 months.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed metastatic colorectal cancer of the parenchyma of the liver

    • No evidence of extrahepatic disease (limited resectable extrahepatic disease allowed)
  • Unresectable liver metastasis, as defined by the following:

    • More than 3 sites of disease
    • Bilobar disease
    • Tumor abutting major vascular or ductal structures
  • Measurable disease
  • No biopsy-proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices, or collateral vessels around organs drained by the portal venous system

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Platelet count greater than 100,000/mm^3
  • Hematocrit greater than 27.0%
  • WBC greater than 3,000/mm^3

Hepatic:

  • Bilirubin less than 2.0 mg/dL
  • PT no greater than 2 seconds over upper limit of normal
  • Elevations in transaminases secondary to metastatic disease allowed
  • No veno-occlusive disease
  • No active chronic hepatitis

    • Hepatitis B or C allowed provided there is no evidence of cirrhosis

Renal:

  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular:

  • No ischemic cardiac disease
  • No prior congestive heart failure with LVEF less than 40%

Pulmonary:

  • No chronic obstructive pulmonary disease or other chronic pulmonary disease with pulmonary function test less than 50% of predicted

Other:

  • No active infections
  • Not pregnant or nursing
  • Negative pregnancy test
  • Weight greater than 30 kg

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy for disease and recovered

Chemotherapy:

  • At least 4 weeks since prior chemotherapy for disease and recovered
  • No prior intrahepatic artery infusion therapy with floxuridine

Endocrine therapy:

  • Not specified

Radiotherapy:

  • At least 4 weeks since prior radiotherapy for disease and recovered

Surgery:

  • Not specified

Other:

  • No concurrent immunosuppressive drugs
  • No concurrent chronic anticoagulants
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00020501


Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Institutes of Health Clinical Center (CC)
National Cancer Institute (NCI)
Investigators
Study Chair: H. Richard Alexander, MD, FACS NCI - Surgery Branch
  More Information

ClinicalTrials.gov Identifier: NCT00020501     History of Changes
Obsolete Identifiers: NCT00011427
Other Study ID Numbers: 010093
NCI-01-C-0093
CDR0000068562
First Submitted: July 11, 2001
First Posted: January 27, 2003
Last Update Posted: March 8, 2012
Last Verified: March 2012

Keywords provided by National Institutes of Health Clinical Center (CC):
stage IV colon cancer
stage IV rectal cancer
recurrent colon cancer
recurrent rectal cancer
liver metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Irinotecan
Fluorouracil
Melphalan
Floxuridine
Levoleucovorin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs