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Isolated Hepatic Perfusion With Melphalan Followed by Combination Chemotherapy in Treating Patients With Unresectable Liver Metastases From Colorectal Cancer

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. Identifier: NCT00103298
Recruitment Status : Completed
First Posted : February 8, 2005
Last Update Posted : June 20, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as melphalan, leucovorin, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways may kill more tumor cells.

PURPOSE: This phase II trial is studying how well isolated hepatic perfusion with melphalan followed by combination chemotherapy works in treating patients with unresectable liver metastases from colorectal cancer.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Cancer Drug: FOLFOX regimen Drug: fluorouracil Drug: isolated perfusion Drug: leucovorin calcium Drug: melphalan Drug: oxaliplatin Phase 2

Detailed Description:



  • Determine the response and duration of response in patients with previously untreated unresectable liver metastases secondary to colorectal cancer treated with isolated hepatic perfusion with melphalan followed by leucovorin calcium, oxaliplatin, and fluorouracil.


  • Determine the patterns of recurrence (liver vs systemic) in patients treated with this regimen.
  • Determine progression-free and overall survival of patients treated with this regimen.
  • Correlate health-related quality of life with length of survival of patients treated with this regimen.

OUTLINE: Patients undergo exploratory laparotomy. Patients with evidence of carcinomatosis not previously visualized on scans but found on surgical exploration are removed from the study. All other patients then undergo isolated hepatic perfusion (IHP). Once IHP is established, melphalan is administered intra-arterially over 3-5 minutes and then circulated throughout the liver for 1 hour. Approximately 6-12 weeks later, patients receive systemic chemotherapy comprising oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1-2. Courses with systemic chemotherapy repeat every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, after laparotomy, after completion of systemic chemotherapy, and then every 6 months thereafter.

After completion of study treatment, patients are followed every 3 months for 1 year, every 3-4 months for 2 years, and then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2-3 years.

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Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Isolated Hepatic Perfusion (IHP) and Systemic FOLFOX4 for Subjects With Metastatic Unresectable Colorectal Cancers of the Liver With ≥ 40% Hepatic Tumor Burden
Study Start Date : December 2004
Actual Study Completion Date : July 2006

Primary Outcome Measures :
  1. Response and duration of response

Secondary Outcome Measures :
  1. Patterns of recurrence
  2. Progression-free and overall survival
  3. Correlation of health-related quality of life with length of survival

Information from the National Library of Medicine

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


  • Histologically or cytologically confirmed colorectal cancer

    • Metastatic disease limited to the parenchyma of the liver

      • No evidence of unresectable extrahepatic disease by preoperative radiology

        • Limited extra-hepatic disease and dominant life-limiting liver disease allowed provided extra-hepatic sites are treatable by local ablative measures (e.g., surgical resection or external beam radiotherapy)
  • At least 40% hepatic replacement by tumor by axial CT scan or MRI
  • Unresectable liver metastases, defined by 1 of the following:

    • More than 3 sites of disease in the liver
    • Bilobar disease
    • Tumor abutting major vascular or ductal structures
  • Measurable disease
  • Previously untreated disease



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


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


  • Bilirubin < 2.0 mg/dL
  • PT < 2 seconds above upper limit of normal
  • Elevated transaminase levels allowed if due to liver metastases
  • No cirrhosis by biopsy
  • No significant portal hypertension as manifested by any of the following:

    • Ascites
    • Esophageal varices by endoscopy
    • Significant collateral vessels around the organs drained by the portal venous system by radiography
  • No chronic active hepatitis

    • Hepatitis B and C surface antigen negative
  • No history of veno-occlusive disease


  • Creatinine ≤ 1.5 mg/dL OR
  • Creatinine clearance > 60 mL/min


  • No ischemic cardiac disease
  • No history of congestive heart failure
  • LVEF > 40% by echocardiogram or stress thallium scan (for patients with cardiac disease)


  • No chronic obstructive pulmonary disease or other chronic pulmonary disease
  • Pulmonary function tests ≥ 50% of predicted (for patients with pulmonary disease)


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Weight > 30 kg
  • No active infection
  • No peripheral neuropathy ≥ grade 2


Biologic therapy

  • Not specified


  • Prior adjuvant chemotherapy (including leucovorin calcium, oxaliplatin, and fluorouracil) allowed provided it was administered > 6 months before liver metastases were diagnosed

Endocrine therapy

  • Not specified


  • More than 4 weeks since prior radiotherapy for this malignancy and recovered


  • Not specified


  • No concurrent chronic anticoagulation therapy
  • No concurrent immunosuppressive drugs

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 identifier (NCT number): NCT00103298

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United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Cancer Institute (NCI)
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Study Chair: H. Richard Alexander, MD, FACS NCI - Surgery Branch
Layout table for additonal information Identifier: NCT00103298    
Obsolete Identifiers: NCT00096889
Other Study ID Numbers: CDR0000409754
First Posted: February 8, 2005    Key Record Dates
Last Update Posted: June 20, 2013
Last Verified: February 2006
Keywords provided by National Cancer Institute (NCI):
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
liver metastases
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Protective Agents
Vitamin B Complex