Adjuvant Hepatic Arterial Infusion and Combination Chemotherapy in Treating Patients With Resectable Hepatic Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to find the highest dose that can be given safely to people who have had liver disease resected. This is a Phase I study. The goal of a phase I study is to find a safe dose range based on side effects. The drugs that will be given by vein are OXALIPLATIN (Oxali) plus 5-FLUOROURACIL and LEUCOVORIN (5FU and LV). This is systemic chemotherapy, since it goes to the whole body. The drugs that will be placed in the pump are FLOXURIDINE (FUDR) and DEXAMETHASONE. (The dexamethasone is not an anti-tumor drug; it helps protect healthy liver tissue from possible side effects of the FUDR.) This is the regional chemotherapy, since it goes only to the liver. The researchers have studied these drugs and know the best doses of each when they are used in patients who have not had liver resections. We do not yet know how the drugs work with each other in patients with a liver resection. This study will tell us the best doses of each drug when they are given over the same period of time.

Official Title
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A Phase I Study Of Hepatic Arterial Infusion With Floxuridine And Dexamethasone In Combination With Intravenous Oxaliplatin Plus 5-Fluorouracil And Leucovorin As Adjuvant Treatment After Resection Of Hepatic Metastases From Colorectal Cancer

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: FOLFOX regimen
* Drug: dexamethasone
* Drug: floxuridine
* Drug: fluorouracil
* Drug: leucovorin calcium
* Drug: oxaliplatin
* Procedure: adjuvant therapy
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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Subject Inclusion Criteria: History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed at MSKCC. Potentially completely resectable hepatic metastases without current evidence of other metastatic disease. Abdominal and pelvic CT scans and chest CT or x-ray within 6 weeks prior to registration. (MRI of abdomen may be substituted for CT of abdomen.) Lab values within 14 days prior to registration: WBC ≥ 3.0 K/ul ANC >1.5 K/ul Platelets ≥ 100 K/ul Total bilirubin ≤ 1.5 mg/dl. Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to registration to this study. KPS ≥ 60% Signed informed consent. Subject Exclusion Criteria: Prior radiation to the liver. (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration.) Active infection, ascites, hepatic encephalopathy Prior oxaliplatin or cisplatin or HAI FUDR Female patients who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adjuvant Hepatic Arterial Infusion & Combination Chemotherapy<br>This is a Phase I study with the primary objective of defining the maximum tolerated dose of hepatic arterial floxuridine (FUDR) and dexamethasone (Dex) given via an implanted pump in combination with intravenous oxaliplatin plus systemic fluorouracil (5FU)/leucovorin (LV) in the adjuvant setting after resection of hepatic metastases from colorectal cancer. A total of eleven dose levels will be considered. | Drug: FOLFOX regimen<br> <br> Drug: dexamethasone<br> <br> Drug: floxuridine<br> <br> Drug: fluorouracil<br> <br> Drug: leucovorin calcium<br> <br> Drug: oxaliplatin<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: conventional surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | 2 years | 
| Correlate thymidylate synthase, dihydropyrimidine dehydrogenase, and ERCC-1 with survival and recurrence as measured by normal and tumor liver tissue |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver metastases, stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum, recurrent colon cancer, recurrent rectal cancer