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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00103298
First received: February 7, 2005
Last updated: June 18, 2013
Last verified: February 2006
  Purpose

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 Intervention Phase
Colorectal Cancer
Metastatic Cancer
Drug: FOLFOX regimen
Drug: fluorouracil
Drug: isolated perfusion
Drug: leucovorin calcium
Drug: melphalan
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response and duration of response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patterns of recurrence [ Designated as safety issue: No ]
  • Progression-free and overall survival [ Designated as safety issue: No ]
  • Correlation of health-related quality of life with length of survival [ Designated as safety issue: No ]

Study Start Date: December 2004
Study Completion Date: July 2006
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

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

Hepatic

  • 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

Renal

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

Cardiovascular

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

Pulmonary

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

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • 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

Radiotherapy

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

Surgery

  • Not specified

Other

  • No concurrent chronic anticoagulation therapy
  • No concurrent immunosuppressive drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103298

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Study Chair: H. Richard Alexander, MD, FACS NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00103298     History of Changes
Obsolete Identifiers: NCT00096889
Other Study ID Numbers: CDR0000409754, NCI-05-C-0025
Study First Received: February 7, 2005
Last Updated: June 18, 2013
Health Authority: United States: Federal Government

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:
Colorectal Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases
Fluorouracil
Levoleucovorin
Melphalan
Alkylating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on November 20, 2014