Clinical trial NCT01042691: Isolated Liver Perfusion With Oxaliplatin
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unresectable Colorectal Liver Metastases
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: The Pittsburgh Foundation
name: Sanofi
First posted: 2010-01-05
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: To determine the maximum tolerated dose and dose limiting toxicity of oxaliplatin delivered via isolated hepatic perfusion (IHP).
timeFrame: 12 months
Secondary outcomes:
measure: 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.
timeFrame: 2-3 years
measure: To determine the tissue absorption of oxaliplatin in normal liver versus tumor during IHP.
timeFrame: 12 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Presbyterian
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers, Hillman Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Shadyside
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: David L Bartlett, M.D.
role: PRINCIPAL_INVESTIGATOR
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