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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Metastatic Cancer; Colorectal Cancer

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00059930

MSKCC-03005

03-005

Details and patient eligibility

About

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.

Enrollment: 38 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

Adjuvant Hepatic Arterial Infusion & Combination Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: oxaliplatin

Drug: fluorouracil

Drug: dexamethasone

Drug: leucovorin calcium

Procedure: conventional surgery

Drug: FOLFOX regimen

Drug: floxuridine

Procedure: adjuvant therapy