Isolated Liver Perfusion With Oxaliplatin

December 19, 2017 updated by: David Bartlett

A Phase I Trial of Isolated Hepatic Perfusion With Oxaliplatin Followed by Hepatic Arterial Infusion of FUDR and Leucovorin for Patients With Unresectable Colorectal Liver Metastases

The primary goal of this research study is to determine a safe dose for the drug oxaliplatin when delivered by isolated hepatic perfusion. The second goal of this research study is to determine if isolated hepatic perfusion with oxaliplatin can improve the efficacy of standard hepatic arterial infusional (HAI) therapy with floxuridine (FUDR)/leucovorin.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Cancer Centers, Hillman Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Shadyside

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients will be included that are scheduled to undergo surgery for placement of hepatic arterial infusion pump for HAI therapy and
  • Histologically or cytologically proven measurable metastatic colorectal cancer limited to the parenchyma of the liver with no evidence of unresectable extrahepatic disease by preoperative radiological studies. Limited resectable extrahepatic disease is acceptable.
  • No chemotherapy, radiotherapy, or biologic therapy for their malignancy in the 4 weeks prior to the liver perfusion and must have recovered from all side effects.
  • An ECOG performance standard of 0, 1 or 2 for 24 hours prior to surgery.
  • Adequate hepatic function as evidenced by bilirubin < 2.0 mg/dL and a PT < 2 seconds greater than the upper limit of normal.
  • Age equal to 18 years or older and greater than 30 kg.
  • Platelet counts greater than 100,000, a hematocrit > 27.0, a white blood count > 3000/microliter, and a creatinine less than or equal to 1.5 mg/dL or a creatinine clearance of > 60 mL/min. Patients with elevations in hepatic transaminases secondary to the presence of metastatic disease in the liver are eligible.
  • Aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks and willing to sign an informed consent.
  • The disease in the liver must be considered unresectable as defined by greater than three sites of disease in the liver, bilobar disease, and tumor abutting major vascular or ductal structures making anatomic resection with preservation of liver function impossible.

Exclusion Criteria:

  • Pregnant patients and nursing mothers will be excluded due to the unknown effects of oxaliplatin on the fetus or newborn
  • Patients taking immunosuppressive drugs or on chronic anticoagulation will not be eligible.
  • Patients with active infections are not eligible.
  • Patients with biopsy proven cirrhosis or evidence of significant portal hypertension manifested by ascites, esophageal varices on endoscopy, or radiologic studies showing significant collateral vessels around the organs drained by the portal venous system will be excluded.
  • Patients with ischemic cardiac disease or history of congestive heart failure with an LVEF < 40% will be excluded.
  • Patients with COPD or other chronic pulmonary disease with PFT's indicating an FEV< 50% predicted for age will be excluded.
  • Patients with a history of veno-occlusive disease of the liver are ineligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oxaliplatin
Subjects who are planning to undergo surgery for placement of HAI therapy pump will be considered for enrollment. Standard HAI therapy requires a laparotomy and placement of an intrahepatic arterial catheter that is connected to one of several commercially available subcutaneous electronic pumps. The pump is then used to deliver FUDR and Leucovorin directly to the liver, usually beginning four weeks after surgery and lasts on average for a period of six to twelve months after the study. This study will examine the addition of a one hour isolated hepatic perfusion with oxaliplatin to this standard treatment
Drug: Oxaliplatin
The starting dose of oxaliplatin administered via isolated hepatic perfusion will be the safe tolerated dose of intra-arterial infusion and pharmacokinetics from intravenous studies. The dose will be 5 mg/m2 and will be escalated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the maximum tolerated dose and dose limiting toxicity of oxaliplatin delivered via isolated hepatic perfusion (IHP).
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To determine if isolated hepatic perfusion with oxaliplatin can increase the response rate, duration of response and survival of patients being treated with standard HAI with FUDR when compared to historical controls.
Time Frame: 2-3 years
2-3 years
To determine the tissue absorption of oxaliplatin in normal liver versus tumor during IHP.
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

David Bartlett

Collaborators

Sanofi
The Pittsburgh Foundation

Investigators

  • Principal Investigator: David L Bartlett, M.D., University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2003

Primary Completion (Actual)

November 1, 2011

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

January 4, 2010

First Submitted That Met QC Criteria

January 4, 2010

First Posted (Estimate)

January 5, 2010

Study Record Updates

Last Update Posted (Actual)

December 20, 2017

Last Update Submitted That Met QC Criteria

December 19, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 02-135

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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