A Phase I Study of Isolated Hepatic Perfusion With Escalating Dose Melphalan Followed by Postoperative Hepatic Arterial Floxuridine and Leucovorin for Metastatic Unresectable Colorectal Cancers of the Liver

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ClinicalTrials.gov Identifier: NCT00001576

Recruitment Status : Completed

First Posted : November 4, 1999

Last Update Posted : March 4, 2008

Sponsor:

Information provided by:

National Institutes of Health Clinical Center (CC)

Study Description

Brief Summary:

Patients with unresectable metastatic colorectal cancer confined to the liver will undergo a 1 hour hyperthermic isolated hepatic perfusion (IHP) with escalating dose melphalan. Postoperatively, patients will be treated with hepatic arterial infusion of floxuridine (FUDR), 0.2 mg/kg/day and leucovorin (LV), 15 mg/M2/day as a 2-week continuous infusion regimen. Hepatic and systemic toxicity, response to treatment, duration of response, and survival will be followed.

Condition or disease	Intervention/treatment	Phase
Colorectal Neoplasm Liver Neoplasm Neoplasm Metastasis	Drug: Melphalan Drug: Floxuridine Drug: Leucovorin	Phase 1

Detailed Description:

Patients with unresectable metastatic colorectal cancer confined to the liver will undergo a 1 hour hyperthermic isolated hepatic perfusion (IHP) with escalating dose melphalan. Postoperatively, patients will be treated with hepatic arterial infusion of floxuridine (FUDR), 0.2 mg/kg/day and leucovorin (LV), 15 mg/M(2)/day as a 2-week continuous infusion regimen. Hepatic and systemic toxicity, response to treatment, duration of response, and survival will be followed.

Study Design

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Study Type :	Interventional (Clinical Trial)
Enrollment :	28 participants
Primary Purpose:	Treatment
Official Title:	A Phase I Study of Isolated Hepatic Perfusion With Escalating Dose Melphalan Followed by Postoperative Hepatic Arterial Floxuridine and Leucovorin for Metastatic Unresectable Colorectal Cancers of the Liver
Study Start Date :	July 1997
Study Completion Date :	March 2002

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Colorectal Cancer Liver Cancer

Drug Information available for: Floxuridine Leucovorin Melphalan Melphalan hydrochloride

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Patients must not have been previously treated with intrahepatic artery infusional therapy using FUDR.

Patients mush have had no chemotherapy, radiotherapy or biologic therapy for their malignancy in the month prior to the liver perfusion and must have recovered from all side effects.

Patients must have an ECOG performance standard of 0, 1 or 2 on the day prior to treatment.

Patients must have adequate hepatic function as evidence by bilirubin less than 2.0 and a PT and PTT that are within 1-2 seconds of the upper normal limit.

Patients must not have biopsy proven cirrhosis or evidence of significant portal hypertension by history, endoscopy, or radiologic studies.

Patients must not have a history of congestive heart failure with an LVEF less than 40%.

Patients must not have COPD or other chronic pulmonary disease with PFT's less than 50% predicted for age.

Patients must be 18 years of age or older.

Patients must have a platelet count greater than 100,000 a Hct greater than 27.0, a white blood count greater than 3000/micro liters, and a creatinine less than or equal to 1.5 or a creatinine clearance of greater than 60 ml/min.

Patients must not be pregnant or nursing.

Patients must not be taking immunosuppressive drugs or on chronic anticoagulation.

Patients must not have an active infection.

Patients must not have severe allergic reactions to iodine contrast which can not be controlled by premedication with antihistamines and steroids.

Patients must not have HIV disease.

Patients must be aware of the neoplastic nature of his/her illness, the experimental nature of the therapy, alternative treatments, potential benefits, and risks. The patient must be willing to sign an informed consent.

Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT00001576

Locations

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United States, Maryland
National Cancer Institute (NCI)
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

Publications:

Kemeny N, Conti JA, Cohen A, Campana P, Huang Y, Shi WJ, Botet J, Pulliam S, Bertino JR. Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma. J Clin Oncol. 1994 Nov;12(11):2288-95.

Kemeny N, Seiter K, Conti JA, Cohen A, Bertino JR, Sigurdson ER, Botet J, Chapman D, Mazumdar M, Budd AJ. Hepatic arterial floxuridine and leucovorin for unresectable liver metastases from colorectal carcinoma. New dose schedules and survival update. Cancer. 1994 Feb 15;73(4):1134-42.

Chang AE, Schneider PD, Sugarbaker PH, Simpson C, Culnane M, Steinberg SM. A prospective randomized trial of regional versus systemic continuous 5-fluorodeoxyuridine chemotherapy in the treatment of colorectal liver metastases. Ann Surg. 1987 Dec;206(6):685-93.

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ClinicalTrials.gov Identifier:	NCT00001576 History of Changes
Other Study ID Numbers:	970111 97-C-0111
First Posted:	November 4, 1999 Key Record Dates
Last Update Posted:	March 4, 2008
Last Verified:	March 2002

Keywords provided by National Institutes of Health Clinical Center (CC):


Regional Therapy Organ Perfusion Metastases Hyperthermia

Additional relevant MeSH terms:

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Colorectal Neoplasms Neoplasm Metastasis Liver Neoplasms Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Neoplastic Processes	Pathologic Processes Liver Diseases Melphalan Floxuridine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites

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