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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00059930

Collaborator

National Cancer Institute (NCI) (NIH), University of Medicine and Dentistry of New Jersey (Other)

Enrollment

Locations

Arm

245

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Drug: FOLFOX regimen Drug: dexamethasone Drug: floxuridine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

38 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2003

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adjuvant Hepatic Arterial Infusion & Combination Chemotherapy 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 Drug: dexamethasone Drug: floxuridine Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery

Arm

Intervention/Treatment

Experimental: Adjuvant Hepatic Arterial Infusion & Combination Chemotherapy

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

Drug: dexamethasone

Drug: floxuridine

Drug: fluorouracil

Drug: leucovorin calcium

Drug: oxaliplatin

Procedure: adjuvant therapy

Procedure: conventional surgery

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065