Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combined With Combination Chemotherapy in Treating Patients With Colorectal Cancer That Has Spread to the Liver

NCT00492999 | Active Not Recruiting Phase 2

• 2 other identifiers: 06-075MSKCC-06075
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

Brief Summary

RATIONALE: Hepatic arterial infusion uses a catheter to carry tumor-killing substances directly into the liver. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving floxuridine and dexamethasone directly into the arteries around the tumor together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well hepatic arterial infusion with floxuridine and dexamethasone works when given together with combination chemotherapy in treating patients with colorectal cancer that has spread to the liver.

Conditions

Colorectal Cancer; Metastatic Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum; liver metastases

Outcome Measures

Primary Outcomes (1)

• Resectability rate

  2 years

Secondary Outcomes (4)

• Antitumor activity

  2 years

• Response rate

  2 years

• Median time to progression

  2 years

• Survival

  2 years

Study Arms (2)

Group 1

EXPERIMENTAL

Patients receive hepatic arterial infusion (HAI) therapy comprising floxuridine and dexamethasone continuously on days 1-14. Patients also receive oxaliplatin IV over 2 hours and irinotecan hydrochloride IV over 30 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: dexamethasone; Drug: floxuridine; Drug: irinotecan hydrochloride; Drug: oxaliplatin

Group 2

EXPERIMENTAL

Patients receive HAI therapy as in group 1. Patients also receive irinotecan hydrochloride IV over 30 minutes and leucovorin calcium IV over 30 minutes on days 1 and 15 and fluorouracil IV continuously over 48 hours on days 1, 2, 15, and 16. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: dexamethasone; Drug: floxuridine; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium

Interventions

dexamethasone DRUG

Given by hepatic arterial infusion

Group 1; Group 2

floxuridine DRUG

Given by hepatic arterial infusion

Group 1; Group 2

fluorouracil DRUG

Given IV

Group 2

irinotecan hydrochloride DRUG

Given IV

Group 1; Group 2

leucovorin calcium DRUG

Given IV

Group 2

oxaliplatin DRUG

Given IV

Group 1

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed colorectal adenocarcinoma metastatic to the liver * Previously treated or untreated disease * No clinical or radiographic evidence of extrahepatic disease * Primary tumor may be present at study registration provided it is not obstructing the intestinal lumen or is significantly bleeding * If present, the primary tumor will be resected at the time of pump placement * Must have inoperable liver metastases confirmed by 2-3 hepatobiliary surgeons and the assigned radiologist * Liver metastases \< 70% of the liver parenchyma * Inoperable liver metastases is defined by one of the following: * More than 6 metastases in a single lobe with one lesion ≥ 5 cm * At least 6 metastases distributed diffusely in both lobes of the liver * When a margin-negative resection would require resection of all three hepatic veins, both portal veins, or the retrohepatic vena cava * Requires a resection that leaves \< 2 hepatic segments (not including the caudate lobe) behind with adequate arterial or portal inflow, venous outflow, and biliary drainage * No ascites or hepatic encephalopathy * No history of primary CNS tumors PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * WBC ≥ 3,000/mm\^3 * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * INR \< 1.5 * Hemoglobin ≥ 9 g/dL * Creatinine ≤ 1.5 mg/dL * Total bilirubin ≤ 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Physically able to tolerate major partial hepatectomy * No active infection * No concurrent active malignancies, except potentially resectable primary colorectal tumor * No bleeding diathesis or coagulopathy * No history of serious systemic disease, including any of the following: * Myocardial infarction within the past 6 months * Uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg on medication) * Unstable angina * New York Heart Association class II-IV congestive heart failure * Unstable symptomatic arrhythmia requiring medication * Chronic atrial arrhythmia (i.e., atrial fibrillation or paroxysmal supraventricular tachycardia) allowed * Peripheral vascular disease ≥ grade 2 * No serious or nonhealing active wound, ulcer, or bone fracture * No history of seizures not well controlled with standard medical therapy * No stroke or transient ischemic attack within the past 6 months * No concurrent obstruction of the gastrointestinal or genitourinary tract PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior radiotherapy to the pelvis * Prior chemotherapy allowed * No prior radiotherapy, hepatic thermal ablation, or resection (other than biopsy) to the liver * No prior floxuridine * No prior hepatic arterial infusion * No concurrent chronic aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Memorial Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Location

Memorial Sloan Kettering Cancer Center@Phelps Memorial Hospital

Sleepy Hollow, New York, United States

Location

Related Publications (2)

• Correa-Gallego C, Gavane S, Grewal R, Cercek A, Klimstra DS, Gewirtz AN, Kingham TP, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR, Kemeny N, D'Angelica MI. Prospective evaluation of 18F-fluorodeoxyglucose positron emission tomography in patients receiving hepatic arterial and systemic chemotherapy for unresectable colorectal liver metastases. HPB (Oxford). 2015 Jul;17(7):644-50. doi: 10.1111/hpb.12421. Epub 2015 May 23.

  PMID: 26010778 DERIVED

• D'Angelica MI, Correa-Gallego C, Paty PB, Cercek A, Gewirtz AN, Chou JF, Capanu M, Kingham TP, Fong Y, DeMatteo RP, Allen PJ, Jarnagin WR, Kemeny N. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes. Ann Surg. 2015 Feb;261(2):353-60. doi: 10.1097/SLA.0000000000000614.

  PMID: 24646562 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis; Colonic Neoplasms; Rectal Neoplasms

Interventions

Dexamethasone; Floxuridine; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Deoxyuridine; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Uracil; Pyrimidinones; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Michael D'Angelica, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Nancy E. Kemeny, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2007
• First Posted: June 27, 2007
• Study Start: May 1, 2007
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

US (5)