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

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00059930

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Chemoprotective drugs such as dexamethasone may protect normal cells from the side effects of chemotherapy. Combining more than one chemotherapy drug and giving them after surgery may kill any remaining tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining adjuvant hepatic arterial infusion with combination chemotherapy in treating patients who have resectable hepatic (liver) metastases from colorectal cancer.

Condition	Intervention	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 I

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer Surgery

Drug Information available for: Dexamethasone Floxuridine Fluorouracil Leucovorin Citrovorum factor Dexamethasone acetate Oxaliplatin Doxiproct plus Leucovorin Calcium Dexamethasone Sodium Phosphate Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose [ Designated as safety issue: Yes ]
Correlate thymidylate synthase, dihydropyrimidine dehydrogenase, and ERCC-1 with survival and recurrence as measured by normal and tumor liver tissue [ Designated as safety issue: No ]

Estimated Enrollment:	78
Study Start Date:	January 2003
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of intravenous oxaliplatin and fluorouracil when administered with leucovorin calcium in combination with hepatic arterial infusion of floxuridine and dexamethasone in patients with resectable hepatic metastases secondary to colorectal adenocarcinoma.
Correlate thymidylate synthase, dihydropyrimidine dehydrogenase, and excision repair cross-complementing genes in normal and tumor liver tissue with survival and recurrence in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil.

Patients undergo surgery for resection of the liver and placement of the hepatic artery pump.

Hepatic arterial infusion (HAI) therapy: Approximately 4 weeks after surgery, patients receive HAI therapy comprising floxuridine and dexamethasone on day 1.
Systemic chemotherapy: Patients receive oxaliplatin IV and leucovorin calcium IV over 120 minutes and fluorouracil IV bolus (followed by a 48-hour infusion of fluorouracil) on days 15 and 29.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Treatment repeats every 36 days for up to 6 courses in the absence of disease recurrence or unacceptable toxicity.

Patients are followed every 3 months after the completion of treatment.

PROJECTED ACCRUAL: A total of 2-78 patients will be accrued for this study within 12-16 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed colorectal adenocarcinoma metastatic to the liver
- No clinical or radiographic evidence of extrahepatic disease
Potentially completely resectable hepatic metastases without current evidence of other metastatic disease
No ascites

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 1.5 mg/dL
No hepatic encephalopathy

Renal

Not specified

Other

Not pregnant or nursing
Negative pregnancy test
No active infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

At least 3 weeks since prior chemotherapy
No prior oxaliplatin
No prior cisplatin
No prior hepatic arterial infusion of floxuridine

Endocrine therapy

Not specified

Radiotherapy

At least 4 weeks since prior radiotherapy to the pelvis
No prior radiotherapy to the liver

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00059930

Locations

United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Clinical Trials Office - Cancer Institute of New Jersey 732-235-8675
United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Nancy E. Kemeny, MD 212-639-8068

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Nancy E. Kemeny, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000298988, MSKCC-03005
Study First Received:	May 6, 2003
Last Updated:	July 22, 2009
ClinicalTrials.gov Identifier:	NCT00059930 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

liver metastases
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon

adenocarcinoma of the rectum
recurrent colon cancer
recurrent rectal cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Dexamethasone
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Gastrointestinal Diseases
Colonic Diseases
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Leucovorin
Antiemetics
Hormones
Rectal Diseases

Neoplastic Processes
Oxaliplatin
Neoplasms by Site
Pathologic Processes
Vitamins
Therapeutic Uses
Neoplasm Metastasis
Micronutrients
Dexamethasone acetate
Vitamin B Complex
Digestive System Neoplasms
Antineoplastic Agents, Hormonal
Floxuridine
Growth Substances
Gastrointestinal Agents

ClinicalTrials.gov processed this record on November 09, 2009