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

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

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Drug: fluorouracil; Drug: leucovorin calcium; Drug: dexamethasone; Procedure: adjuvant therapy; Drug: oxaliplatin; Procedure: conventional surgery; Drug: FOLFOX regimen; Drug: floxuridine

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: fluorouracil; Drug: leucovorin calcium; Drug: dexamethasone; Procedure: adjuvant therapy; Drug: oxaliplatin; Procedure: conventional surgery; Drug: FOLFOX regimen; Drug: floxuridine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: National Cancer Institute (NCI); University of Medicine and Dentistry of New Jersey
• Investigators: Study Chair: Nancy E. Kemeny, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2003
• Primary Completion (Actual): March 24, 2025
• Study Completion (Actual): March 24, 2025

Study Registration Dates

• First Submitted: May 6, 2003
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimated): May 7, 2003

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon; recurrent colon cancer; recurrent rectal cancer; liver metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Calcium-Regulating Hormones and Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antimetabolites, Antineoplastic; Antimetabolites; Micronutrients; Protective Agents; Antidotes; Vitamin B Complex; Vitamins; Oxaliplatin; Dexamethasone; Calcium; Fluorouracil; Leucovorin; Levoleucovorin; Floxuridine
• Other Study ID Numbers: 03-005; MSKCC-03005