Isolated Liver Perfusion With Oxaliplatin

This study has been completed.
Sponsor:
Collaborators:
The Pittsburgh Foundation
Sanofi-Synthelabo
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01042691
First received: January 4, 2010
Last updated: December 8, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Unresectable Colorectal Liver Metastases
Drug: Oxaliplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To determine the maximum tolerated dose and dose limiting toxicity of oxaliplatin delivered via isolated hepatic perfusion (IHP). [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • To determine the tissue absorption of oxaliplatin in normal liver versus tumor during IHP. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: May 2003
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01042691

Locations
United States, Pennsylvania
UPMC Presbyterian
Pittsburgh, Pennsylvania, United States, 15213
UPMC Shadyside
Pittsburgh, Pennsylvania, United States, 15232
UPMC Cancer Centers, Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
The Pittsburgh Foundation
Sanofi-Synthelabo
Investigators
Principal Investigator: David L Bartlett, M.D. University of Pittsburgh
  More Information

Publications:
Kemeny,M.M., S.Adak, and S.Lipsitz. 1999. Results of the intergroup [Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) prospective randomized study of surgery alone versus continuous hepatic artery infusion of FuDR and continuous systemic infusion of 5FU after hepatic resection for colorectal liver metastases. Proc ASCO 18:1012.
Alexander,H.R., D.L.Bartlett, D.L.Fraker, S.K.Libutti, T.Moser, and S.A.Rosenberg. 1997. Results of a Phase II study of isolated hepatic perfusion (IHP) with tumor necrosis factor (TNF) and melphalan for unresectable primary or metastatic cancer confined to the liver. Proc.Soc.Surg.Oncol. 6:8. (Abstr.)

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01042691     History of Changes
Other Study ID Numbers: 02-135
Study First Received: January 4, 2010
Last Updated: December 8, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasm Metastasis
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Oxaliplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014